Updated on 2025/01/20

写真a

 
KOBAYASHI Hiroya
 
Organization
School of Medicine Medical Course Basic Medicine Pathology[Immuno Pathology]
External link

Degree

  • 旭川医科大学大学院医学研究科修了 博士（医学） ( 1995.3   旭川医科大学 )

Research Areas

  • Life Science / Experimental pathology

  • Life Science / Immunology

  • Life Science / Human pathology

Education

  • Asahikawa Medical College   Graduate School, Division of Medicine

    - 1995.3

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    Country： Japan

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  • Asahikawa Medical College   Graduate School, Division of Medicine

    - 1995

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  • Asahikawa Medical College   Faculty of Medicine

    - 1991.3

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    Country： Japan

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  • Asahikawa Medical College   Faculty of Medicine   医学

    - 1991

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Research History

  • Asahikawa Medical College   Professor

    2011.7

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Professional Memberships

Studying abroad experiences

  • 1998.8 - 2001.3   メイヨークリニック (Mayo Clinic)   助手

Papers

  • Immunotherapy targeting tumor-associated antigen in a mouse model of head and neck cancer. Reviewed

    Kono M., Wakisaka R., Komatsuda H., Hayashi R., Kumai T., Yamaki H., Sato R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Kishibe K., Kobayashi H., Hayashi T., Takahara M.

    Head Neck   46 ( 8 )   2056 - 2067   2024.8

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  • NF9 peptide specific cytotoxic T lymphocyte clone cross react to Y453F mutation of SARS-CoV-2 virus spike protein. Reviewed International journal

    Aiko Murai, Terufumi Kubo, Takayuki Ohkuri, Junko Yanagawa, Yuki Yajima, Akemi Kosaka, Dongliang Li, Toshihiro Nagato, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Takeshi Nagasaki, Yoshihiko Hirohashi, Hiroya Kobayashi, Toshihiko Torigoe

    Immunological medicine   47 ( 2 )   93 - 99   2024.7

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    The recognition by cytotoxic T cells (CTLs) is essential for the clearance of SARS-CoV-2 virus-infected cells. Several viral proteins have been described to be recognized by CTLs. Among them, the spike (S) protein is one of the immunogenic proteins. The S protein acts as a ligand for its receptors, and several mutants with different affinities for its cognate receptors have been reported, and certain mutations in the S protein, such as L452R and Y453F, have been found to inhibit the HLA-A24-restricted CTL response. In this study, we conducted a screening of candidate peptides derived from the S protein, specifically targeting those carrying the HLA-A24 binding motif. Among these peptides, we discovered that NF9 (NYNYLYRLF) represents an immunogenic epitope. CTL clones specific to the NF9 peptide were successfully established. These CTL clones exhibited the ability to recognize endogenously expressed NF9 peptide. Interestingly, the CTL clone demonstrated cross-reactivity with the Y453F peptide (NYNYLFRLF) but not with the L452R peptide (NYNYRYRLF). The CTL clone was able to identify the endogenously expressed Y453F mutant peptide. These findings imply that the NF9-specific CTL clone possesses the capability to recognize and respond to the Y453F mutant peptide.

    DOI： 10.1080/25785826.2024.2304363

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  • Soluble CD27 as a predictive biomarker for intra-tumoral CD70/CD27 interaction in nasopharyngeal carcinoma. Reviewed

    Nagato T., Komatsuda H., Hayashi R., Takahara M., Ujiie N., Kosaka A., Ohkuri T., Oikawa K., Sato R., Wakisaka R., Kono M., Yamaki H., Ohara K., Kumai T., Kishibe K., Katada A., Hayashi T., Kobayashi H.

    Cancer Sci.   115 ( 4 )   1073 - 1084   2024

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  • SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity. International journal

    Yuki Yajima, Akemi Kosaka, Takayuki Ohkuri, Yoshihiko Hirohashi, Dongliang Li, Takeshi Nagasaki, Toshihiro Nagato, Toshihiko Torigoe, Hiroya Kobayashi

    Heliyon   9 ( 9 )   e20192   2023.9

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    The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on the mRNA of the SARS-CoV-2 spike protein have been developed to induce both cellular and humoral immunity against SARS-CoV-2, there have been some concerns raised about their high cost, particularly in developing countries. In the present study, we aim to identify an immunogenic peptide in the SARS-CoV-2 spike protein to activate cellular immunity, particularly CD4+ helper T lymphocytes (Th cells), which are a commander of immune system. SARS-CoV-2 spike protein-derived peptides Spike448-477 and Spike489-513(N501Y)-specific CD4+ Th cell lines were generated by repetitive stimulation of healthy donor-derived CD4+T-cells with each peptide. Their HLA-restrictions were addressed by using blocking antibodies against HLA and HLA-transfected L-cells. The epitopes of Spike448-477-specific CD4+ Th cell lines were defined using a series of 7-14-mer overlapping truncated peptides and alanine-substituted epitope peptides. To address responsiveness of these CD4+ Th cell lines to several SARS-CoV-2 variants, we stimulated the CD4+ Th cell lines with mutated peptides. We addressed whether these identified peptides were useful for monitoring T-cell-based immune responses in vaccinated donors using the IFN-γ ELISpot assay. The Spike448-477 peptide was found to be a promiscuous peptide presented by HLA- DRB1*08:02, DR53, and DPB1*02:02. Although HLA-DPB1*02:02-restricted CD4+ Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4+ Th cells were not affected by any mutant peptides. We developed two tetramers to detect HLA-DRB1*08:02/Spike449-463- and Spike449-463(L452R/Y453F)-recognizing CD4+ Th cells. Spike489-513(N501Y) peptide was also a promiscuously presented to HLA-DRB1*09:01 and DRB1*15:02. The T-cell responses specific to both peptides Spike448-477 and Spike489-513 were detected in PBMCs after vaccinations. In addition, we observed that the Spike448-477 peptide activated both CD8+ T-cells and CD4+ Th cells in individuals receiving mRNA vaccines. SARS-CoV-2 spike protein-derived peptides, Spike448-477 and Spike489-513, include several epitopes that are presented by multiple HLA-class II alleles to activate CD4+ Th cells, which are considered useful for monitoring the establishment of acquired immunity after vaccination.

    DOI： 10.1016/j.heliyon.2023.e20192

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  • Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer. Reviewed

    Yamaki H., Kono M., Wakisaka R., Komatsuda H., Kumai T., Hayashi R., Sato R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Kishibe K., Takahara M., Hayashi T., Kobayashi H., Katada A.

    Cancer Immunol Immunother.   72 ( 8 )   2799 - 2812   2023.8

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  • Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy. Reviewed

    Nagato T., Komatsuda H., Hayashi R., Takahara M., Kishibe K., Yasuda S., Yajima Y., Kosaka A., Ohkuri T., Oikawa K., Harabuchi S., Kono M., Yamaki H., Wakisaka R., Hirata- Nozaki Y., Ohara K., Kumai T., Katada A., Hayashi T., Harabuchi Y., Kobayashi H.

    Cancer Immunol Immunother.   27 ( 2 )   2087 - 2098   2023.7

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  • Celecoxib promotes the efficacy of STING-targeted therapy by increasing antitumor CD8+ T-cell functions via modulating glucose metabolism of CD11b+Ly6G+ cells. Reviewed

    Kosaka A., Yajima Y., Yasuda S., Komatsuda H., Nagato T., Oikawa K., Kobayashi H., Ohkuri T.

    Int J Cancer   152 ( 8 )   1685 - 1697   2023.2

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  • MAPK inhibition augments the T-cell response against HOXB7-expressing tumor through HLA upregulation. Reviewed

    Komatsuda H., Wakisaka R., Kono M., Kumai T., Hayashi R., Yamaki H., Sato R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Takahara M., Katada A., Kobayashi H.

    Cancer Sci.   114 ( 2 )   399 - 409   2023.2

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  • A tumor metastasis-associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity. Reviewed

    Yajima Y., Kosaka A., Ishibashi K., Yasuda S., Komatsuda H., Nagato T., Oikawa K., Kitada M., Takekawa M., Kumai T., Ohara K., Ohkuri T., Kobayashi H.

    Cancer Sci.   113 ( 8 )   2526 - 2535   2022.8

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  • IFN-α/β-mediated NK2R expression is related to the malignancy of colon cancer cells. Reviewed

    Xiang H., Toyoshima Y., Shen W., Wang X., Okada N., Kii S., Sugiyama K., Nagato T., Kobayashi H., Ikeo K., Hashimoto S., Tanino M., Taketomi A., Kitamura H.

    Cancer Sci.   113 ( 8 )   2513 - 2525   2022.8

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  • An infantile case of hereditary folate malabsorption with sudden development of pulmonary hemorrhage: a case report. Reviewed

    Sakurai Y., Toriumi N., Sarashina T., Ishioka T., Nagata M., Kobayashi H., Azuma H.

    J Med Case Rep.   16 ( 1 )   268   2022.6

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  • A case of primary histiocytic sarcoma arising from a neck lymph node. Reviewed

    Kubota A., Ishida Y., Hashiguchi J., Sato R., Wada T., Bandoh N., Sato K., Kobayashi H., Nishihara H., Harabuchi Y.

    Ear Nose Throat J.   2022.4

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  • Immunomodulation via FGFR inhibition augments FGFR1 targeting T-cell based antitumor immunotherapy for head and neck squamous cell carcinoma. Reviewed

    Kono M., Komatsuda H., Yamaki H., Kumai T., Hayashi R., Wakisaka R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Kishibe K., Takahara M., Katada A., Hayashi T., Kobayashi H., Harabuchi Y.

    Oncoimmunology   11 ( 1 )   2021619   2022.1

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  • CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes

    Akemi Kosaka, Kei Ishibashi, Toshihiro Nagato, Hidemitsu Kitamura, Yukio Fujiwara, Syunsuke Yasuda, Marino Nagata, Shohei Harabuchi, Ryusuke Hayashi, Yuki Yajima, Kenzo Ohara, Takumi Kumai, Naoko Aoki, Yoshihiro Komohara, Kensuke Oikawa, Yasuaki Harabuchi, Masahiro Kitada, Hiroya Kobayashi, Takayuki Ohkuri

    Journal of Experimental Medicine   218 ( 11 )   2021.9

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    Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic antiCD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy.

    DOI： 10.1084/jem.20200792

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  • Severe spruelike enteropathy and collagenous colitis caused by olmesartan. Reviewed

    Kaneko S., Matsuda K., Mizuta Y., Shiratori S., Kishi K., Nakamura A., Yagisawa M., Ehira N., Uebayashi M., Kobayashi H.

    BMC Gastroenterol.   21 ( 1 )   350   2021.9

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  • A stealth antigen SPESP1, which is epigenetically silenced in tumors, is a suitable target for cancer immunotherapy. International journal

    Akemi Kosaka, Yuki Yajima, Mayumi Hatayama, Katsuya Ikuta, Takaaki Sasaki, Noriko Hirai, Syunsuke Yasuda, Marino Nagata, Ryusuke Hayashi, Shohei Harabuchi, Kenzo Ohara, Mizuho Ohara, Takumi Kumai, Kei Ishibashi, Yui Hirata-Nozaki, Toshihiro Nagato, Kensuke Oikawa, Yasuaki Harabuchi, Esteban Celis, Toshikatsu Okumura, Yoshinobu Ohsaki, Hiroya Kobayashi, Takayuki Ohkuri

    Cancer science   112 ( 7 )   2705 - 2713   2021.7

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    Recent studies have revealed that tumor cells decrease their immunogenicity by epigenetically repressing the expression of highly immunogenic antigens to survive in immunocompetent hosts. We hypothesized that these epigenetically hidden "stealth" antigens should be favorable targets for cancer immunotherapy due to their high immunogenicity. To identify these stealth antigens, we treated human lung cell line A549 with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5Aza) and its prodrug guadecitabine for 3 d in vitro and screened it using cDNA microarray analysis. We found that the gene encoding sperm equatorial segment protein 1 (SPESP1) was re-expressed in cell lines including solid tumors and leukemias treated with 5Aza, although SPESP1 was not detected in untreated tumor cell lines. Using normal human tissue cDNA panels, we demonstrated that SPESP1 was not detected in normal human tissue except for testis and placenta. Moreover, we found using immunohistochemistry SPESP1 re-expression in xenografts in BALB/c-nu/nu mice that received 5Aza treatment. To assess the antigenicity of SPESP1, we stimulated human CD4+ T-cells with a SPESP1-derived peptide designed using a computer algorithm. After repetitive stimulation, SPESP1-specific helper T-cells were obtained; these cells produced interferon-γ against HLA-matched tumor cell lines treated with 5Aza. We also detected SPESP1 expression in freshly collected tumor cells derived from patients with acute myeloid leukemia or lung cancer. In conclusion, SPESP1 can be classified as a stealth antigen, a molecule encoded by a gene that is epigenetically silenced in tumor cells but serves as a highly immunogenic antigen suitable for cancer immunotherapy.

    DOI： 10.1111/cas.14973

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  • The feasibility of circulating tumor DNA analysis as a marker of recurrence in triple-negative breast cancer. Reviewed

    Okazaki S., Sasaki T., Yasuda S., Abe M., Yoshida N., Yoshida R., Ishibashi K., Minami Y., Okumura S., Chiba S., Takei H., Hayashi R., Nagato T., Kobayashi H., Sugitani A., Ono Y., Mizukami Y., Kitada M., Ohsaki Y.

    Oncol Lett.   21 ( 5 )   430   2021.5

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  • Interruption of MDM2 signaling augments MDM2-targeted T cell-based antitumor immunotherapy through antigen-presenting machinery. International journal

    Michihisa Kono, Takumi Kumai, Ryusuke Hayashi, Hidekiyo Yamaki, Hiroki Komatsuda, Risa Wakisaka, Toshihiro Nagato, Takayuki Ohkuri, Akemi Kosaka, Kenzo Ohara, Kan Kishibe, Miki Takahara, Akihiro Katada, Tatsuya Hayashi, Esteban Celis, Hiroya Kobayashi, Yasuaki Harabuchi

    Cancer immunology, immunotherapy : CII   2021.4

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    Identification of immunogenic tumor antigens, their corresponding T cell epitopes and the selection of effective adjuvants are prerequisites for developing effective cancer immunotherapies such as therapeutic vaccines. Murine double minute 2 (MDM2) is an E3 ubiquitin-protein ligase that negatively regulates tumor suppressor p53. Because MDM2 overexpression serves as a poor prognosis factor in various types of tumors, it would be beneficial to develop MDM2-targeted cancer vaccines. In this report, we identified an MDM2-derived peptide epitope (MDM232-46) that elicited antigen-specific and tumor-reactive CD4+ T cell responses. These CD4+ T cells directly killed tumor cells via granzyme B. MDM2 is expressed in head and neck cancer patients with poor prognosis, and the T cells that recognize this MDM2 peptide were present in these patients. Notably, Nutlin-3 (MDM2-p53 blocker), inhibited tumor cell proliferation, was shown to augment antitumor T cell responses by increasing MDM2 expression, HLA-class I and HLA-DR through class II transactivator (CIITA). These results suggest that the use of this MDM2 peptide as a therapeutic vaccine combined with MDM2 inhibitors could represent an effective immunologic strategy to treat cancer.

    DOI： 10.1007/s00262-021-02940-5

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  • A critical role of STING-triggered tumor- migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment. Reviewed

    Nagata M., Kosaka A., Yajima Y., Yasuda S., Ohara M., Ohara K., Harabuchi S., Hayashi R., Funakoshi H., Ueda J., Kumai T., Nagato T., Oikawa K., Harabuchi Y., Esteban C., Ohkuri T., Kobayashi H.

    Cancer Immunol Immunother.   2021.1

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  • Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma. International journal

    Ryusuke Hayashi, Toshihiro Nagato, Takumi Kumai, Kenzo Ohara, Mizuho Ohara, Takayuki Ohkuri, Yui Hirata-Nozaki, Shohei Harabuchi, Akemi Kosaka, Marino Nagata, Yuki Yajima, Syunsuke Yasuda, Kensuke Oikawa, Michihisa Kono, Kan Kishibe, Miki Takahara, Akihiro Katada, Tatsuya Hayashi, Esteban Celis, Yasuaki Harabuchi, Hiroya Kobayashi

    Oncoimmunology   10 ( 1 )   1856545 - 1856545   2020.12

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    Placenta-specific 1 (PLAC1) is expressed primarily in placental trophoblasts but not in normal tissues and is a targetable candidate for cancer immunotherapy because it is a cancer testis antigen known to be up-regulated in various tumors. Although peptide epitopes capable of stimulating CD8 T cells have been previously described, there have been no reports of PLAC1 CD4 helper T lymphocyte (HTL) epitopes and the expression of this antigen in head and neck squamous cell carcinoma (HNSCC). Here, we show that PLAC1 is highly expressed in 74.5% of oropharyngeal and 51.9% of oral cavity tumors from HNSCC patients and in several HNSCC established cell lines. We also identified an HTL peptide epitope (PLAC131-50) capable of eliciting effective antigen-specific and tumor-reactive T cell responses. Notably, this peptide behaves as a promiscuous epitope capable of stimulating T cells in the context of more than one human leukocyte antigen (HLA)-DR allele and induces PLAC1-specific CD4 T cells that kill PLAC1-positive HNSCC cell lines in an HLA-DR-restricted manner. Furthermore, T-cells reactive to PLAC131-50 peptide were detected in the peripheral blood of HNSCC patients. These findings suggest that PLAC1 represents a potential target antigen for HTL based immunotherapy in HNSCC.

    DOI： 10.1080/2162402X.2020.1856545

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  • Contribution of long-chain fatty acid to induction of myeloid-derived suppressor cell (MDSC)-like cells - induction of MDSC by lipid vesicles (liposome). Reviewed

    Yoshida Y., Nagamori T., Ishibazawa E., Kobayashi H., Kure T., Sakai H., Takahashi D., Fujihara M., Azuma H.

    Immunopharmacol Immunotoxicol.   42 ( 6 )   614 - 624   2020.12

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  • Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer. Reviewed

    Ohara M., Ohara K., Kumai T., Ohkuri T., Nagato T., Hirata-Nozaki Y., Kosaka A., Nagata M., Hayashi R., Harabuchi S., Yajima Y., Oikawa K., Harabuchi Y., Sumi Y., Furukawa H., Kobayashi H.

    Cancer Immunol Immunother.   69 ( 6 )   989 - 999   2020.6

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  • Intratumoral STING activations overcome negative impact of cisplatin on antitumor immunity by inflaming tumor microenvironment in squamous cell carcinoma. International journal

    Shohei Harabuchi, Akemi Kosaka, Yuki Yajima, Marino Nagata, Ryusuke Hayashi, Takumi Kumai, Kenzo Ohara, Toshihiro Nagato, Kensuke Oikawa, Mizuho Ohara, Yasuaki Harabuchi, Takayuki Ohkuri, Hiroya Kobayashi

    Biochemical and biophysical research communications   522 ( 2 )   408 - 414   2020.2

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    Although cisplatin (CDDP) has been used as a major chemotherapeutic drug for head and neck squamous cell carcinoma (HNSCC), its impact on T-cell functions is controversial. Therefore, we investigated the immunologic effects of CDDP and antitumor effects by combination therapy of CDDP with a ligand for stimulator of interferon genes, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Direct impacts of CDDP on T-cell functions were addressed by comparing T-cell functions between human subjects treated and untreated with CDDP. The immune responses and the efficacy of combination therapy using CDDP and cGAMP were assessed using BALB/c mice inoculated with mouse squamous cell carcinoma (SCC) cell lines. CDDP inhibited T-cell proliferation in a dose-dependent manner. T-cell functions of CDDP-treated HNSCC patients were comparable to those of healthy donors and CDDP-untreated HNSCC patients. In the mice bearing SCC cell lines, combination therapy using CDDP and cGAMP enhanced the gene expressions of CXCL9 and CXCL10 in the tumor tissues and inhibited tumor growth. The antitumor effect was cancelled by anti-CXCR3 monoclonal antibody. These findings suggest that the combination therapy using CDDP and an immunomodulating drug like cGAMP would be a rational cancer immunotherapy for patients with HNSCC.

    DOI： 10.1016/j.bbrc.2019.11.107

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  • 融合遺伝子ETV6-Xを認めた顎下腺分泌癌例． Reviewed

    河野通久, 石田芳也, 和田哲治, 熊井琢美, 長門利純, 片岡俊朗, 加藤生真, 西原弘治, 小林博也, 原渕保明

    耳鼻臨床   113 ( 12 )   787 - 792   2020

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  • PD-L1-specific helper T-cells exhibit effective antitumor responses: new strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma. International journal

    Yui Hirata-Nozaki, Takayuki Ohkuri, Kenzo Ohara, Takumi Kumai, Marino Nagata, Shohei Harabuchi, Akemi Kosaka, Toshihiro Nagato, Kei Ishibashi, Kensuke Oikawa, Naoko Aoki, Mizuho Ohara, Yasuaki Harabuchi, Yuji Uno, Hidehiro Takei, Esteban Celis, Hiroya Kobayashi

    Journal of translational medicine   17 ( 1 )   207 - 207   2019.6

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    BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) originates from squamous epithelium of the upper aerodigestive tract and is the most common malignancy in the head and neck region. Among HNSCCs, oropharynx squamous cell carcinoma (OSCC) has a unique profile and is associated with human papillomavirus infection. Recently, anti-programmed cell death-1 monoclonal antibody has yielded good clinical responses in recurrent and/or metastatic HNSCC patients. Therefore, programmed death-ligand 1 (PD-L1) may be a favorable target molecule for cancer immunotherapy. Although PD-L1-expressing malignant cells could be targeted by PD-L1-specific CD8+ cytotoxic T lymphocytes, it remains unclear whether CD4+ helper T lymphocytes (HTLs) recognize and kill tumor cells in a PD-L1-specific manner. METHODS: The expression levels of PD-L1 and HLA-DR were evaluated using immunohistochemical analyses. MHC class II-binding peptides for PD-L1 were designed based on computer algorithm analyses and added into in vitro culture of HTLs with antigen-presenting cells to evaluate their stimulatory activity. RESULTS: We found that seven of 24 cases of OSCC showed positive for both PD-L1 and HLA-DR and that PD-L1241-265 peptide efficiently activates HTLs, which showed not only cytokine production but also cytotoxicity against tumor cells in a PD-L1-dependent manner. Also, an adoptive transfer of the PD-L1-specific HTLs significantly inhibited growth of PD-L1-expressing human tumor cell lines in an immunodeficient mouse model. Importantly, T cell responses specific for the PD-L1241-265 peptide were detected in the HNSCC patients. CONCLUSIONS: The cancer immunotherapy targeting PD-L1 as a helper T-cell antigen would be a rational strategy for HNSCC patients.

    DOI： 10.1186/s12967-019-1957-5

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  • Cyclin-dependent kinase 1 and survivin as potential therapeutic targets against nasal natural killer/T-cell lymphoma. International journal

    Toshihiro Nagato, Seigo Ueda, Miki Takahara, Kan Kishibe, Yuki Komabayashi, Takumi Kumai, Kenzo Ohara, Yui Hirata-Nozaki, Shohei Harabuchi, Ryusuke Hayashi, Takayuki Ohkuri, Michele Bernasconi, David Nadal, Hiroya Kobayashi, Yasuaki Harabuchi

    Laboratory investigation; a journal of technical methods and pathology   99 ( 5 )   612 - 624   2019.5

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    Nasal natural killer/T-cell lymphoma (NNKTL) is closely associated with Epstein-Barr virus (EBV) and is characterized by poor prognosis, resulting from rapid progression of lesions in the affected organs. Recent data have shown that NNKTL is associated with the aberrant expression of cyclin-dependent kinase 1 (CDK1) and its downstream target survivin, but little is known about the functional roles of CDK1 and survivin in NNKTL. In the current study, we show that knockdown of the EBV-encoded oncoprotein latent membrane protein 1 (LMP1) induces downregulation of CDK1 and survivin in NNKTL cells. Immunohistochemistry detected CDK1 and survivin expression in LMP1-positive cells of NNKTL biopsy specimens. Inhibition of CDK1 and survivin in NNKTL cells with several inhibitors led to a dose-dependent decrease in cell proliferation. In addition, the Sp1 inhibitor mithramycin, which can downregulate both CDK1 and survivin, significantly suppressed the growth of established NNKTL in a murine xenograft model. Our results suggest that LMP1 upregulation of CDK1 and survivin may be essential for NNKTL progression. Furthermore, targeting CDK1 and survivin with Sp1 inhibitors such as mithramycin may be an effective approach to treat NNKTL, which is considered to be a treatment-refractory lymphoma.

    DOI： 10.1038/s41374-018-0182-9

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  • Targeting phosphorylated p53 to elicit tumor-reactive T helper responses against head and neck squamous cell carcinoma Reviewed

    Kenzo Ohara, Takayuki Ohkuri, Takumi Kumai, Toshihiro Nagato, Yui Hirata-Nozaki, Kei Ishibashi, Akemi Kosaka, Marino Nagata, Shohei Harabuchi, Mizuho Ohara, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi

    Oncoimmunology   7 ( 9 )   e1466771.   2018.8

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    DOI： 10.1080/2162402X.2018.1466771

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  • Sustained persistence of IL2 signaling enhances the antitumor effect of peptide vaccines through T-cell expansion and preventing PD-1 inhibition. Reviewed

    Sultan H., Kumai T., Fesenkova VI, Fan AE, Wu J., Cho HI, Kobayashi H., Harabuchi Y., Celis E.

    Cancer Immunol Res.   6 ( 5 )   617 - 627   2018.5

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  • Effects of STING stimulation on macrophages: STING agonists polarize into "classically" or "alternatively" activated macrophages? Invited Reviewed

    Ohkuri T., Kosaka A., Nagato T., Kobayashi H.

    Hum Vaccin Immunother   14 ( 2 )   285 - 287   2018.2

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  • 鼻性NK/T細胞リンパ腫に対する革新的免疫療法の開発 Invited Reviewed

    長門利純, 熊井琢美, 高原 幹, 大栗敬幸, 小林博也

    耳鼻免疫アレルギー   2018

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  • 【血管炎とアレルギー疾患 -内因性・外因性アジュバントの関わり-】 癌ワクチン療法における免疫アジュバント Invited Reviewed

    長門利純, 熊井琢美, 大栗敬幸, 小林博也, 原渕保明

    アレルギー免疫   2018

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  • Intratumoral injection of IFN-β induces chemokine production in melanoma and augments the therapeutic efficacy of anti-PD-L1 mAb. Reviewed

    Uehara J., Ohkuri T., Kosaka A., Ishibashi K., Hirata Y., Ohara K., Nagato T., Oikawa K., Aoki N., Harabuchi Y., Ishida-Yamamoto A., Kobayashi H.

    Biochem Biophys Res Commun.   490 ( 2 )   521 - 527   2017.8

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  • Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. International journal

    Toshihiro Nagato, Takayuki Ohkuri, Kenzo Ohara, Yui Hirata, Kan Kishibe, Yuki Komabayashi, Seigo Ueda, Miki Takahara, Takumi Kumai, Kei Ishibashi, Akemi Kosaka, Naoko Aoki, Kensuke Oikawa, Yuji Uno, Naoko Akiyama, Masatoshi Sado, Hidehiro Takei, Esteban Celis, Yasuaki Harabuchi, Hiroya Kobayashi

    Cancer immunology, immunotherapy : CII   66 ( 7 )   877 - 890   2017.7

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    Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patients. Most significantly, soluble PD-L1 (sPD-L1) was present in sera of NNKTL patients at higher levels as compared to healthy individuals and the levels of serum sPD-L1 in patients positively correlated with the expression of PD-L1 in lymphoma cells of tumor tissues. In addition, the high-sPD-L1 group of patients showed significantly worse prognosis than the low-sPD-L1 group. Furthermore, we confirmed that membrane and soluble PD-L1 was expressed on the surface and in the culture supernatant, respectively, of NNKTL cell lines. The expression of PD-L1 was observed in tumor tissues and sera from a murine xenograft model inoculated with an NNKTL cell line. Our results suggest that sPD-L1 could be a prognostic predictor for NNKTL and open up the possibility of immunotherapy of this lymphoma using PD-1/PD-L1 axis inhibitors.

    DOI： 10.1007/s00262-017-1987-x

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  • Intratumoral administration of cGAMP transiently accumulates potent macrophages for anti-tumor immunity at a mouse tumor site. International journal

    Takayuki Ohkuri, Akemi Kosaka, Kei Ishibashi, Takumi Kumai, Yui Hirata, Kenzo Ohara, Toshihiro Nagato, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi

    Cancer immunology, immunotherapy : CII   66 ( 6 )   705 - 716   2017.6

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    Stimulator of IFN genes (STING) spontaneously contributes to anti-tumor immunity by inducing type I interferons (IFNs) following sensing of tumor-derived genomic DNAs in the tumor-bearing host. Although direct injection of STING ligands such as cyclic diguanylate monophosphate (c-di-GMP) and cyclic [G(2',5')pA(3',5')p] (cGAMP) into the tumor microenvironment exerts anti-tumor effects through strong induction of type I IFNs and activation of innate and adaptive immunity, the precise events caused by STING in the tumor microenvironment remain to be elucidated. We describe here our finding that a CD45+ CD11bmid Ly6C+ cell subset transiently accumulated in mouse tumor microenvironment of 4T1 breast cancer, squamous cell carcinomas, CT26 colon cancer, or B16F10 melanoma tissue after intratumoral injection of cGAMP. The accumulated cells displayed a macrophage (M ) phenotype since the cells were positive for F4/80 and MHC class II and negative for Ly6G. Intratumoral cGAMP treatment did not induce Mφ accumulation in STING-deficient mice. Depletion of CD8+ T cell using anti-CD8 mAb impaired the anti-tumor effects of cGAMP treatment. Depletion of the Mφ using clodronate liposomes impaired the anti-tumor effects of cGAMP treatment. Functional analysis indicated that the STING-triggered tumor-migrating Mφ exhibited phagocytic activity, production of tumor necrosis factor alpha TNFα), and high expression levels of T cell-recruiting chemokines, Cxcl10 and Cxcl11, IFN-induced molecules, MX dynamin-like GTPase 1 (Mx1) and 2'-5' oligoadenylate synthetase-like 1 (Oasl1), nitric oxide synthase 2 (Nos2), and interferon beta 1 (Ifnb1). These results indicate that the STING-triggered tumor-migrating Mφ participate in the anti-tumor effects of STING-activating compounds.

    DOI： 10.1007/s00262-017-1975-1

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  • Liposomal microparticle injection can induce myeloid-derived suppressor cells (MDSC)-like cells in vivo. Reviewed

    Azuma H., Yoshida Y., Takahashi H., Ishibazawa E., Kobayashi H., Sakai H., Takahashi D., Fujihara M.

    Immunopharmacol Immunotoxicol   5   1 - 8   2017.4

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    DOI： 10.1080/08923973.2017.1306867

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  • Peptide vaccines in cancer-old concept revisited. Invited Reviewed

    Kumai T., Kobayashi H., Harabuchi Y., Celis E.

    Curr Opin Immunol.   45   1 - 7   2017.4

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  • Optimization of Peptide Vaccines to Induce Robust Antitumor CD4 T-cell Responses. Reviewed

    Kumai T., Lee S., Cho HI, Sultan H., Kobayashi H., Harabuchi Y., Celis E.

    Cancer Immunol Res.   5 ( 1 )   72 - 83   2017.1

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    DOI： 10.1158/2326-6066.CIR-16-0194

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  • Visinin-Like Protein-3 Modulates the Interaction Between Cytochrome b (5) and NADH-Cytochrome b (5) Reductase in a Ca(2+)-Dependent Manner. Reviewed

    Oikawa K., Odero GL, Nafez S., Ge N., Zhang D., Kobayashi H., Sate K., Kimura S., Tateno M., Albensi BC

    Cell Biochem Biophys.   74 ( 4 )   449 - 457   2016.12

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  • Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy. International journal

    Kei Ishibashi, Takumi Kumai, Takayuki Ohkuri, Akemi Kosaka, Toshihiro Nagato, Yui Hirata, Kenzo Ohara, Kensuke Oikawa, Naoko Aoki, Naoko Akiyama, Masatoshi Sado, Masahiro Kitada, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi

    Oncoimmunology   5 ( 6 )   e1169356   2016.6

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    Tumor immune escape has been a major problem for developing effective immunotherapy. The human leukocyte antigen G (HLA-G) is a non-classical MHC class I molecule whose primary function is to protect the fetus from the mother's immune system. While HLA-G is hardly found in normal adult tissues, various tumor cells are known to express it, aiding their escape from the immune system. Thus, HLA-G is an attractive immunotherapy target. CD4(+) helper T lymphocytes (HTLs) play an important role in the immune reaction against tumors by assisting in the generation and persistence of CD8(+) cytotoxic T lymphocytes (CTLs) or by displaying direct antitumor effects. We report here that HLA-G expression in breast cancer significantly correlates with a poor prognosis. Also, we describe that the MHC class II-binding peptide HLA-G26-40 was effective in eliciting tumor-reactive CD4(+) T cell responses. Furthermore, treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine increased HLA-G expression in tumors and subsequently enhanced recognition by HLA-G26-40-specific HTLs. These findings predict that a combination immunotherapy targeting HLA-G together with a DNA methyltransferase inhibitor could be useful against some cancers.

    DOI： 10.1080/2162402X.2016.1169356

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  • Assessment of the change in cetuximab induced ADCC activity of NK cells by steroid. Kumai T, Oikawa K, Aoki N, Kimura S, Harabuchi Y, Kobayashi H. Reviewed

    Kumai T., Oikawa K., Aoki N., Kimura S., Harabuchi Y., Kobayashi H.

    Head & Neck   38 ( 3 )   410 - 416   2016.3

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  • Neuroprotective effect of water-dispersible hesperetin in retinal ischemia reperfusion injury. Reviewed

    Shimouchi A., Yokota H., Ono S., Matsumoto C., Tamai T., Takumi H., Narayanan SP, Kimura S., Kobayashi H., Caldwell RB, Nagaoka T., Yoshida A.

    Jpn J Ophthalmol.   60 ( 1 )   51 - 61   2016.1

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  • Novel targets for natural killer/T-cell lymphoma immunotherapy. Reviewed

    Kumai T., Kobayashi H., Harabuchi Y.

    Immunotherapy   8 ( 1 )   45 - 55   2016.1

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    DOI： 10.2217/imt.15.103

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  • Neuropeptide signaling through neurokinin-1 and neurokinin-2 receptors augments antigen presentation by human dendritic cells. Reviewed

    Ohtake J., Kaneumi S., Tanino M., Kishikawa T., Terada S., Sumida K., Masuko K., Ohno Y., Kita T., Iwabuchi S., Shinohara T., Tanino Y., Takemura T., Tanaka S., Kobayashi H., Kitamura H.

    J Allergy Clin Immunol.   136 ( 6 )   1690 - 1694   2015.12

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    DOI： 10.1016/j.jaci.2015.06.050

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  • Targeting HER-3 to elicit antitumor helper T cells against head and neck squamous cell carcinoma. International journal

    Takumi Kumai, Takayuki Ohkuri, Toshihiro Nagato, Yoshinari Matsuda, Kensuke Oikawa, Naoko Aoki, Shoji Kimura, Esteban Celis, Yasuaki Harabuchi, Hiroya Kobayashi

    Scientific reports   5   16280 - 16280   2015.11

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    HER-3 expression has been reported to act as an important oncoprotein in head and neck squamous cell carcinoma. This protein is known to control tumor proliferation and acquisition of resistance by tumor cells towards EGFR inhibitors, therefore, development of a HER-3-targeted therapy is desirable. In this study, we found that HER-3 expression on tumor cells was increased after EGFR inhibition. To establish a novel therapeutic approach for HER-3-positive head and neck carcinoma, we identified a HER-3 helper epitope that could elicit effective helper T cell responses to the naturally processed HER-3-derived epitope presented in a HER-3 expressing tumors. This epitope induced potent cytolytic activity of CD4 T cells against such tumor cells. Moreover, pan HER-family tyrosine kinase inhibitor augmented the responses of HER-3-reactive CD4 T cells via upregulation of HLA-DR protein on the surface of tumor cells. Our results supports the validity of CD4 T cell-dependent HER-3-targeted therapy combined with a broad inhibitor of HER-family.

    DOI： 10.1038/srep16280

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  • CCL17 and CCL22/CCR4 signaling is a strong candidate for novel targeted therapy against nasal natural killer/T-cell lymphoma. International journal

    Takumi Kumai, Toshihiro Nagato, Hiroya Kobayashi, Yuki Komabayashi, Seigo Ueda, Kan Kishibe, Takayuki Ohkuri, Miki Takahara, Esteban Celis, Yasuaki Harabuchi

    Cancer immunology, immunotherapy : CII   64 ( 6 )   697 - 705   2015.6

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    Nasal natural killer/T-cell lymphoma (NNKTL) is associated with Epstein-Barr virus and has a poor prognosis because of local invasion and/or multiple dissemination. Various chemokines play a role in tumor proliferation and invasion, and chemokine receptors including the C-C chemokine receptor 4 (CCR4) are recognized as potential targets for treating hematologic malignancies. The aim of the present study was to determine whether specific chemokines are produced by NNKTL. We compared chemokine expression patterns in culture supernatants of NNKTL cell lines with those of other lymphoma or leukemia cell lines using chemokine protein array and ELISA. Chemokine (C-C motif) ligand (CCL) 17 and CCL22 were highly produced by NNKTL cell lines as compared to the other cell lines. In addition, CCL17 and CCL22 were readily observed in the sera of NNKTL patients. The levels of these chemokines were significantly higher in patients than in healthy controls. Furthermore, we detected the expression of CCR4 (the receptor for CCL17 and CCL22) on the surface of NNKTL cell lines and in tissues of NNKTL patients. Anti-CCR4 monoclonal antibody (mAb) efficiently induced antibody-dependent cellular cytotoxicity mediated by natural killer cells against NNKTL cell lines. Our results suggest that CCL17 and CCL22 may be important factors in the development of NNKTL and open up the possibility of immunotherapy of this lymphoma using anti-CCR4 mAb.

    DOI： 10.1007/s00262-015-1675-7

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  • c-Met is a novel tumor associated antigen for T-cell based immunotherapy against NK/T cell lymphoma. Reviewed

    Kumai T., Matsuda Y., Ohkuri T., Oikawa K., Ishibashi K., Aoki N., Kimura S., Harabuchi Y., Celis E., Kobayashi H.

    OncoImmunology   4 ( 2 )   e976077   2015.3

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    DOI： 10.4161/2162402X.2014.976077

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  • c-Met is a novel tumor associated antigen for T-cell based immunotherapy against NK/T cell lymphoma. International journal

    Takumi Kumai, Yoshinari Matsuda, Takayuki Ohkuri, Kensuke Oikawa, Kei Ishibashi, Naoko Aoki, Shoji Kimura, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi

    Oncoimmunology   4 ( 2 )   e976077   2015.2

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    Background: The expression of c-Met and its ligand HGF plays a critical role in cell proliferation and is involved in numerous malignancies. Because c-Met expression and its role in NK/T-cell lymphoma remain unclear, we studied the expression and function of c-Met in NK/T-cell lymphoma cells. In addition, we investigated the possibility that c-Met could function as a tumor-associated antigen for helper T lymphocytes (HTLs). Methods: We evaluated whether HGF and c-Met were expressed in NK/T-cell lymphoma and the capacity of predicted c-Met HTL epitopes to induce antitumor responses in vitro. In addition, c-Met inhibitor was evaluated for the ability to inhibit TGF-β production in tumor and subsequently increase HTL recognition. Results: c-Met and HGF were expressed in NK/T-cell lymphoma cell lines, nasal NK/T-cell lymphoma specimens and patient serum samples. Moreover, HGF was shown to promote NK/T cell lymphoma (NKTCL) proliferation in an autocrine manner. Furthermore, we have identified three novel c-Met HTL epitopes that were restricted by several HLA-DR molecules. Notably, peptide-induced HTL lines directly recognized and killed c-Met expressing NK/T-cell lymphomas and various epithelial solid tumors. The c-Met specific HTLs could also recognize dendritic cells (DCs) pulsed with c-Met expressing tumor cell lysates. In addition, we observed that c-Met inhibition augmented HTL recognition by decreasing TGF-β production by tumor cells. Lastly, autophagy partly regulated the HTL responses against tumors. Conclusions: We identified novel c-Met HTL epitopes that can elicit effective antitumor responses against tumors expressing c-Met. Our results provide the rationale of combining c-Met targeting therapy and immunotherapy for NKTCLs and epithelial tumors.

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  • 腎盂に発生した破骨細胞型巨細胞を伴う尿路未分化癌（Osteoclast-rich undifferentiated carcinoma of the urinary tract)の１例 Reviewed

    菱山真広, 青木直子, 永田真莉乃, 熊井琢美, 大栗敬幸, 及川賢輔, 佐藤啓介, 櫻井宏治, 木村昭治, 小林博也

    診断病理   32 ( 1 )   57 - 61   2015.1

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  • Induction of tumor-reactive T helper responses by a posttranslational modified epitope from tumor protein p53. Reviewed

    Kumai, T., Ishibashi, K., Oikawa, K., Matsuda, Y., Aoki, N., Kimura, S., Hayashi, S., Kitada, M., Harabuchi, Y., Celis, E., Kobayashi, H.

    Cancer Immunol Immunother.   63 ( 5 )   469 - 478   2014.5

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    DOI： 10.1007/s00262-014-1533-z

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  • Clear cell sarcoma-like gastrointestinal tumorの１例 Reviewed

    永田真莉乃, 青木直子, 及川賢輔, 松田佳也, 熊井琢美, 木村昭治, 佐藤啓介, 櫻井宏治, 長谷川匡, 小林博也

    診断病理   31 ( 2 )   147 - 151   2014.4

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  • Tumor-derived TGF-ß and prostaglandin E2 attenuate anti-tumor immune responses in head and neck squamous cell carcinoma treated with EGFR inhibitor. Reviewed

    Kumai T., Oikawa K., Aoki N., Kimura S., Harabuchi Y., Celis E., Kobayashi H.

    J Transl Med.   12 ( 1 )   265   2014

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  • ヘルパー T 細胞と免疫アジュバントを用いた頭頸部癌免疫治療の開発 Invited Reviewed

    熊井琢美, 長門利純, 高原 幹, 小林博也, 原渕保明

    耳鼻免疫アレルギー   32 ( 3 )   185 - 190   2014

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  • EGFR inhibitors augment antitumour helper T-cell responses of HER family-specific immunotherapy. Reviewed

    Kumai T., Matsuda Y., Oikawa K., Aoki N., Kimura S., Harabuchi Y., Celis E., Kobayashi H.

    Br J Cancer   15 ( 109 )   2155 - 2166   2013.10

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  • A naturally processed HLA-DR-bound peptide from the IL-9 receptor alpha of HTLV-1-transformed T cells serves as a T helper epitope. Reviewed

    Kobayashi H., Kumai T., Hayashi S., Matsuda Y., Aoki N., Sato K., Kimura S., Celis E.

    Cancer Immunol Immunother.   61 ( 12 )   2215 - 2225   2012.12

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    DOI： 10.1007/s00262-012-1284-7

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  • ポリスチレンスルホン酸カルシウム内服中に発症した高齢者S状結腸穿孔の２例 Reviewed

    青木直子, 及川賢介, 佐藤啓介, 櫻井宏治, 立野正敏, 小林博也

    診断病理   29 ( 3 )   222 - 226   2012.7

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  • 顆粒細胞様変化を来したCellular dermatofibromaの一例 Reviewed

    青木直子, 皆川智広, 土井春樹, 本間大, 加藤直樹, 櫻井宏治, 佐藤啓介, 山本明美, 小林博也

    日本皮膚病理組織学会誌   28 ( 2 )   57 - 60   2012

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  • Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer Reviewed

    Hayashi S., Kumai T., Matsuda Y., Aoki N., Sato K., Kimura S., Kitada M., Tateno M., Celis E., Kobayashi H.

    J Transl Med.   9   191   2011.11

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    DOI： 10.1186/1479-5876-9-191

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  • 乳腺微小乳頭癌の臨床病理細胞学的検討 Reviewed

    林 諭史, 横山恵, 石川文秋, 山崎知文, 立野正敏, 小林博也

    日本臨床細胞学会雑誌   50 ( 6 )   325 - 331   2011

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  • 乳腺髄様癌の臨床病理細胞学的検討 Reviewed

    林 諭史, 横山恵, 石川文秋, 山崎知文, 立野正敏, 小林博也

    日本臨床細胞学会雑誌   50 ( 3 )   163 - 168   2011

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  • 【症例報告】Cellular neurothekeomaの１例 Reviewed

    青木直子, 小林博也, 佐藤啓介, 藤井 暁, 飛澤 慎一, 立野正敏

    診断病理   27   339 - 342   2010.10

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  • 【症例報告】泡沫状胞体を示す巨細胞癌の形態をとった甲状腺未分化癌の一例 Reviewed

    柳内 充, 高田明生, 青木直子, 安住 誠, 林 諭史, 佐藤啓介, 立野正敏, 小林博也

    診断病理   27   217 - 219   2010.7

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  • Characterization of human CD4 helper T cell responses against Aurora kinase A Reviewed

    Hiroya Kobayashi, Makoto Azumi, Satoshi Hayashi, Keisuke Sato, Naoko Aoki, Shoji Kimura, Hidehiro Kakizaki, Toshihiro Nagato, Yasuaki Harabuchi, Masatoshi Tateno, Esteban Celis

    CANCER IMMUNOLOGY IMMUNOTHERAPY   59 ( 7 )   1029 - 1039   2010.7

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    Aurora kinase A (Aurora-A) is a cell cycle-associated serine-threonine kinase that is overexpressed by various types of cancer and is highly associated with poor prognosis. Since the expression of Aurora-A in normal tissues has been shown to be significantly lower as compared to tumor cells, this protein is being considered as a potential tumor-associated antigen for developing immunotherapies. The goal in the present study was to identify CD4 helper T lymphocyte (HTL) epitopes for Aurora-A for the design of T cell-based immunotherapies against Aurora-A-expressing tumors. Synthetic peptides corresponding to potential HTL epitopes were identified from Aurora-A and used to stimulate CD4 T lymphocytes in vitro to generate antigen-specific HTL clones that were evaluated for antigen specificity, MHC restriction and for their ability to interact with Aurora-A-expressing tumor cells. The results show that two peptides (Aurora-A(161-175) and Aurora-A(233-247)) were effective in generating HTL responses that were restricted by more than one MHC class II allele (i.e., promiscuous responses). The CD4 HTL clones were able to directly recognize Aurora-A-expressing tumor cells in an antigen-specific and MHC class II-restricted manner and some of the clones displayed cytolytic activity toward Aurora-A + tumor cells. Both of these peptides were capable of stimulating in vitro T cell responses in patients with bladder cancer.

    DOI： 10.1007/s00262-010-0826-0

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  • 乳腺管状癌の臨床細胞学的検討 Reviewed

    林諭史, 横山恵, 石川文秋, 山崎知文, 立野正敏, 小林博也

    日本臨床細胞学会雑誌   49 ( 5 )   337 - 339   2010.5

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  • Six-transmembrane epitherial antigen of prostate as an immunotherapeutic target for reanal cell and bladder cancers. Reviewed

    Azumi M., Kobayashi H., Aoki N., Sato K., Kimura S., Kakizaki H., Tateno M.

    J Urol   183 ( (5) )   2036 - 2044   2010.5

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  • 【症例報告】左大腿部に発生した紡錘形細胞型血管腫の１例

    谷口千尋, 青木直子, 安住 誠, 林 諭史, 小林博也, 佐藤啓介, 立野正敏

    診断病理   27   84 - 86   2010.1

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  • Focal adhesion kinase as an immunotherapeutic target Reviewed

    Hiroya Kobayashi, Makoto Azumi, Yuka Kimura, Keisuke Sato, Naoko Aoki, Shoji Kimura, Masaru Honma, Hajime Iizuka, Masatoshi Tateno, Esteban Celis

    CANCER IMMUNOLOGY IMMUNOTHERAPY   58 ( 6 )   931 - 940   2009.6

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    Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune cellular responses.
    To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients.
    Two synthetic peptides, FAK(143-157) and FAK(1,000-1,014), induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient's CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients.
    Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors.

    DOI： 10.1007/s00262-008-0608-0

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  • 【症例報告】指部の線維―骨性偽腫瘍(Fibro-osseous pseudotumor of the digid)の１例 Reviewed

    及川賢輔, 青木直子, 松田佳也, 安住 誠, 林 諭史, 小林博也, 佐藤啓介, 立野正敏, 櫻井宏治

    診断病理   26   54 - 57   2009.4

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  • 【症例報告】乳児線維性過誤腫(Fibrous hamartoma of infancy)の１例 Reviewed

    青木直子, 及川賢輔, 安住 誠, 小林博也, 佐藤啓介, 山尾 健, 皆川知広, 櫻井宏治, 立野正敏

    診断病理   26   168 - 171   2009.4

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  • Focal adhesion kinase as an immunotherapeutic target. Reviewed

    Kobayashi H., Azumi M., Kimura Y., Sato K., Aoki N., Kimura S., Honma M., Iizuka H., Tateno M., Celis E.

    Cancer Immunol Immunother   58   931 - 940   2009.4

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  • Expression and functional role of MDL-1(CLEC5A) in mouse myeloid lineage cells. Reviewed

    Aoki N., Kimura Y., Kimura S., Nagaro T., Azumi M., Kobayashi H., Sato K., Tateno M.

    J Leukoc Biol   85   508 - 517   2009

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  • Promiscuous peptides on the nontypeable haemophilus influenzae p6 outer membrane protein. Reviewed

    Nomura Y., Abe Y., Ishida Y., Kobayashi H., Harabuchi Y.

    J Clin Immunol   28   361 - 369   2008.4

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    DOI： 10.1007/s10875-008-9189-0

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  • 【症例報告】多彩な組織像を呈した硬化性類上皮線維肉腫の1例 Reviewed

    小林博也, 安住 誠, 松田佳也, 青木直子, 佐藤啓介, 櫻井宏治, 立野正敏

    診断病理   25   272 - 275   2008.4

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  • Peptide epitope identification for tumor-reactive CD4 T cells. Reviewed

    Kobayashi H., Celis E.

    Curr Opin Immunol   20   221 - 227   2008.4

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  • Induction of EBV-latent membrane protein 1-specific MHC class II-restricted T-cell responses against natural killer lymphoma cells Reviewed

    Hiroya Kobayashi, Toshihiro Nagato, Nliki Takahara, Keisuke Sato, Shoji Kimura, Naoko Aoki, Makoto Azumi, Masatoshi Tateno, Yasuaki Harabuchi, Esteban Celis

    CANCER RESEARCH   68 ( 3 )   901 - 908   2008.2

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    EBV-encoded latent membrane protein 1 (LMP1) has oncogenic potential and is expressed in many EBV-associated malignancies. Although LMP1 is regarded as a potential tumor-associated antigen for immunotherapy and several LMP1-specific MHC class I-restricted CTL epitopes have been reported, little is known regarding MHC class II-restricted CD4 helper T-lymphocyte (HTL) epitopes for LMP1. The goal of the present studies was to determine whether MHC class II-restricted CD4 T-cell responses could be induced against the LMP1 antigen and to evaluate the antitumor effect of these responses. We have combined the use of a predictive MHC class II binding peptide algorithm with in vitro vaccination of CD4 T cells using candidate peptides to identify naturally processed epitopes derived from LMP1 that elicit immune responses against EBV-expressing tumor cells. Peptide IMP1(159-175) was effective in inducing HTL responses that were restricted by HLA-DR9, HLA-DR53, or HLA-DR15, indicating that this peptide behaves as a promiscuous T-cell epitope. Moreover, LMP1(159-175)-reactive HTL clones directly recognized EBV lymphoblastoid B cells, EBV-infected natural killer (NK)/T-lymphoma cells and naturally processed antigen in the form of LMP1+ tumor cell lysates presented by autologous dendritic cells. Because the newly identified epitope LMP1(159-175) overlaps with an HLA-A2-restricted CTL epitope (LMP1(159-167)), this peptide might have the ability to induce simultaneous CTL and HTL responses against LMP1. Overall, our data should be relevant for the design and optimization of T-cell epitope-based immunotherapy against various EBV-associated malignancies, including NK/T cell lymphomas.

    DOI： 10.1158/0008-5472.CAN-07-3212

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  • 【症例報告】乳癌術後の左上肢リンパ浮腫を背景に発生した血管肉腫（Stewart-Treves症候群）の一例

    青木直子, 小林博也, 佐藤啓介, 櫻井宏治, 立野正敏

    診断病理   24   62 - 65   2007.4

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  • Functional analysis of birch pollen allergen Bet v 1-specific regulatory T cells. Reviewed

    Nagato T., Kobayashi H., Yanai M., Sato K., Aoki N., Oikawa K., Kimura S., Abe Y., Celis E., Harabuchi Y., Tateno M.

    J Immunol   178   1189 - 1198   2007.4

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    DOI： 10.4049/jimmunol.178.2.1189

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  • The role of CCL22/macrophage-derived chemokine in allergic rhinitis. Reviewed

    Yanai M., Sato K., Aoki N., Takiyama Y., Oikawa K., Kobayashi H., Kimura S., Harabuchi Y., Tateno M.

    Clin Immunol   125   291 - 298   2007.4

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  • Defining MHC class II T helper epitopes for WT1 tumor antigen. Reviewed

    Kobayashi H., Nagato T., Aoki N., Sato K., Kimura S., Tateno M., Celis E.

    Cancer Immunol Immunother   55 ( (7) )   850 - 860   2006.7

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  • Identification of human T cell epitopes and highly immunogenic analogue peptides on the non-typeable Hemophilus influenza p6 outer membrane protein. Reviewed

    shida Y., Abe Y., Yanai M., Kobayashi H., Harabuchi Y.

    Clin Immunol   121   90 - 99   2006.4

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  • In vitro peptide immunization of target Tax protein human T-cell leukemia virus type-1-specific CD4+ helper T lymphocytes. Reviewed

    Kobayashi H., Nagato T., Sato K., Aoki N., Kimura S., Tanaka Y., Aizawa H., Tateno M., Celis E.

    Clin Cancer Res   12   3814 - 3822   2006.4

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    DOI： 10.1158/1078-0432.CCR-06-0384

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  • Expression of interleukin9 in nasal natural killer (NK)/T-cell lymphoma cell lines and patients: possible role as an autocrine growth factor. Reviewed

    Nagato T., Kobayashi H., Kishibe K., Takahara M., Ogino T., Ishii H., Oikawa K., Aoki N., Sato K., Kimura S., Shimizu N., Tateno M., Harabuchi Y.

    Clin Cancer Res   11   8285 - 8257   2005.4

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  • Recognition of prostate and breast tumor cells by helper T lymphocytes specific for a prostate and breast tumor-associated antigen, helper T lymphocytes specific for a prostate tumor-associated antigen, TARP. Reviewed

    Kobayashi H., Nagato T., Oikawa K., Sato K., Kimura S., Aoki N., Omiya R., Tateno M., Celis E.

    Clin Cancer Res   11   3869 - 3878   2005.4

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    DOI： 10.1158/1078-0432.CCR-04-2238

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  • Recognition of adult T cell leukemia/lymphoma cells by CD4+ helper T lymphocytes specific for human T cell leukemia virus type I envelope protein. Reviewed

    Kobayashi H., Nagato T., Yanai M., Oikawa K., Sato K., Kimura S., Tateno M., Omiya R., Celis E.

    Clin Cancer Res   10   7053 - 7062   2004.4

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  • Neuronal calcium sensor protein visinin-like protein-3 interacts with microsomal cytochrome b5 in a Ca2+-dependent manner. Reviewed

    Oikawa K., Kimura S., Aoki N., Atsuta Y., Takiyama Y., Nagato T., Yanai M., Kobayashi H., Sato K., Sasajima T., Tateno M.

    J Biol Cem   279   15142 - 15152   2004.4

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    DOI： 10.1074/jbc.M312766200

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  • Identification and characterization of a T-helper peptide from carcinoembrionic antigen. Reviewed

    Ruiz, M., Kobayashi, H., Lasarte, J.J., Prieto, J., Borras-Cuesta, F., Celis, E., Sarobe, P.

    Clin. Cancer Res   ( (10) )   2860 - 2867   2004.4

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  • Decreased expression of retinoid X receptor isoforms in human thyroid carcinomas. Reviewed

    Takiyama Y., Miyokawa N., Sugawara A., Kato S., Ito K., Sato K., Oikawa K., Kobayashi H., Kimura S., Tateno M.

    J Clin Endocrinol Metab   89   5851 - 5856   2004.4

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    DOI： 10.1210/jc.2003-032036

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MISC

  • がんの免疫逃避を打破する治療法の開発

    大栗敬幸, 小坂朱, 小林博也

    バイオサイエンスとインダストリー   2022.7

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  • STINGリガンドと抗CD47抗体の併用によるがん免疫療法

    大栗敬幸, 小坂朱, 小林博也

    週刊 医学のあゆみ   2022.5

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  • CD47遮断は、食細胞を活性化することにより、腫瘍内STINGターゲッティング療法の有効性を高める

    大栗敬幸, 小坂朱, 小林博也

    月刊 臨床免疫・アレルギー科   2022

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  • DNAメチル化によるがん抗原発現の制御

    大栗敬幸, 小坂朱, 小林博也

    月刊 腫瘍内科   2021.5

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  • ステルスがん抗原

    大栗敬幸, 小坂朱, 小林博也

    月刊 臨床免疫・アレルギー科   2021.5

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  • DNA methylation-driven repressin of tumor antigen

    CLINICAL ONCOLOGY   27 ( 5 )   552 - 557   2021.5

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  • Stealth tumor antigen

    Clinical Immunology & Allergoloogy   75 ( 5 )   539 - 543   2021.5

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  • Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner

    Hiroya Kobayashi, Toshihiro Nagato, Keisuke Sato, Naoko Aoki, Shoji Kimura, Masamoto Murakami, Hajime Iizuka, Makoto Azumi, Hidehiro Kakizaki, Masatoshi Tateno, Esteban Celis

    CANCER RESEARCH   67 ( 11 )   5498 - 5504   2007.6

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    The six-transmembrane epithelial antigen of prostate (STEAP) protein is an attractive candidate for T cell-based immunotherapy because it is overexpressed in prostate cancer and various other tumor types. Several peptide epitopes capable of stimulating CTLs that killed STEAP-expressing tumor cells have been described. Our goal was the identification of helper T lymphocyte (HTL) epitopes of STEAP for the optimization of T cell-based immunotherapies against STEAP-expressing malignancies. Candidate HTL epitopes for STEAP were predicted using in silico algorithms for HLA class II-binding peptides and were tested for their ability to elicit HTL responses by in vitro peptide vaccination of CD4 T lymphocytes from healthy individuals and prostate cancer patients. Two peptides (STEAP(102-116) and STEAP(192-206)) were effective in stimulating in vitro antitumor HTL responses in both normal individuals and prostate cancer patients. Notably, both STEAP HTL peptides behaved as promiscuous T-cell epitopes because they stimulated T cells in the context of more than one MHC class II allele. These newly described STEAP HTL epitopes could be of value for the design and optimization of T cell-based immunotherapy against STEAP-expressing tumors.

    DOI： 10.1158/0008-5472.CAN-07-0304

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  • Analysis of anchor residues in a naturally processed HCA-DR53 ligand

    H Kobayashi, T Kokubo, K Abe, K Sato, S Kimura, N Miyokawa, M Katagiri

    IMMUNOGENETICS   44 ( 5 )   366 - 371   1996

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    The peptide motif of the HLA-DR53 (DRB4*0101) molecule, which is associated with autoimmune diseases including Vogt-Koyanagi-Harada's syndrome, was determined by peptide binding assay using human L plastin p581-595 peptide and its substituted analogues. L plastin p581-595 peptide is one of the naturally processed peptides bound to HLA-DR9/DR53 (DRB1*0901/DRB4*0101) molecules. The binding affinity of each peptide to the HLA-DR53 molecule was measured by fluorescence intensity of biotinylated peptides to L cell transfectants expressing HLA-DR53 molecules, followed by treatment with avidin-fluorescence. Binding of biotinylated peptides to HLA-DR53 molecules was not inhibited by all single-alanine-substituted nonbiotinylated peptides, indicating that the replaced position was important for binding to the HLA-DR53 moleule. The inhibitory motif is considered to be an HLA-DR53-specific binding motif, composed of a positively charged residue (Kj at position 1, a hydrophobic residue (T) at position 4, positively charged residue (R or K) at position 8 or 9, and another hydrophobic residue (Ij at position 10. This predicted motif is different from the binding motifs of other HLA-DR molecules. binding peptides in combination with functional analyses, by alignment of sequenced endogeneous peptides, and by the use of an M13 display library (Rammensee et al. 1995; Hammer rt al. 1993, 1993). No sequence information has been reported for naturally occurring HLA-DR53 (DRB4*0101)-associated peptides partly because their expression on the cell surface is relatively low for sequencing endogeneous self-peptides (Kinouchi et al. 1995). Et has been shown that HLA-DR53 is positively associated with Vogt-Koyanagi-Harada's Syndrome in Japanese subjects (Moriuchi et at. 1979). The identification of a peptide motif for HLA-DR53 may help in understanding the mechanisms of this disease. We have previously reported that naturally processed peptides bound to HLA-DR9/DR53 molecules (Futaki et al. 1995). In this report, we determined the peptide which could bind to the HLA-DR53 molecule and we identified a putative HLA-DR53-specific binding motif by a peptide binding assay using L-cell transfectants expressing HLA-DR molecules.

    DOI： 10.1007/s002510050138

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  • INTERFERON-GAMMA-DEPENDENT STIMULATION OF FAS ANTIGEN IN SV40-TRANSFORMED HUMAN KERATINOCYTES - MODULATION OF THE APOPTOTIC PROCESS BY PROTEIN-KINASE-C

    H TAKAHASHI, H KOBAYASHI, Y HASHIMOTO, S MATSUO, H IIZUKA

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   105 ( 6 )   810 - 815   1995.12

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    Fas antigen is a cell membrane protein that has been suggested to mediate apoptosis. Using SV40-transformed human keratinocytes, we investigated the Fas-antigen-dependent apoptotic process. The expression of Fas antigen mRNA was markedly induced by interferon-gamma (IFN-gamma) treatment (500 U/ml). After IFN-gamma treatment in the presence of anti-Fas monoclonal antibody, apoptosis was induced, as detected by the formation of nucleosome-sized fragments of DNA and morphologically by apoptotic cells with round homogeneous nuclear beads detected by acridine orange staining, The apoptotic SV40-transformed keratinocytes were analyzed quantitatively by enzyme-linked immunosorbent assay using antihistone and peroxidase-conjugated anti-DNA antibodies to detect cell death. The IFN-gamma- and anti-Fas antibody-dependent apoptosis was observed by 3 h, and the maximal response was observed by 12 h. The induction of apoptosis was significantly augmented by treatment with 10 ng/ml 12-o-tetradecanoyl-phorbol-13-acetate (TPA). TPA alone had no effect on either Fas antigen expression or on the apoptotic process. Other protein kinase C activators (1-oleoyl-2-acetylglycerol and mezerein) also stimulated IFN-gamma-dependent apoptosis, whereas 4-o-methyl phorbol myristate acetate, a very weak protein kinase C activator, had only a slight effect. The TPA-induced augmentation of apoptosis was inhibited by the protein kinase C inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine dihydrochloride (H-7). However, H-7 inhibited only the TPA-induced augmentation of apoptosis; the basal IFN-gamma- and anti-Fas-dependent apoptosis remained in the presence of H-7. Northern blot analysis revealed that C-jun mRNA was induced by IFN-gamma plus anti-Fas antibody treatment as well as by TPA treatment; the addition of IFN-gamma atone to the incubation medium had no effect on the expression of c-jun mRNA, These results indicate that IFN-gamma induces a Fas-antigen-dependent apoptotic process in SV40-transformed keratinocytes and that TPA augments the process through the activation of protein kinase C.

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  • ANALYSIS OF NATURALLY PROCESSED HUMAN HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN CLASS I-BOUND PEPTIDES FROM HEPATOCELLULAR-CARCINOMA TISSUES IN-VIVO

    H KOBAYASHI, K SATO, N MIYOKAWA, S KIMURA, M NAKASHIMA, M KATAGIRI

    JAPANESE JOURNAL OF CANCER RESEARCH   86 ( 10 )   962 - 968   1995.10

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    Naturally processed self-peptides bound to human histocompatibility leukocyte antigens (HLA) class I molecules of human hepatocellular carcinoma tissues (HLA-A2.1, -B44, -B13) in vivo were isolated for sequence analysis. Acid-eluted peptides were subjected to reversed-phase high-performance liquid chromatographic separation and single-fraction sequencing was performed by Edman degradation. The peptides were found to be octamers or nonamers and they were derived from the processing of intracellular proteins. Three independent sequences were obtained from HLA-A2.1 molecules. One of the peptides showed sequence homology to the hepatitis B virus (HBV) pre-S protein, one to aldehyde dehydrogenase, and the other to no known protein. Two independent sequences were obtained from HLA-B44, B13 molecules: one showed sequence homology to the human c-abl protein, the other showed no homology to any known protein. A synthetic biotinylated peptide based on the HBV pre-S peptide sequence was confirmed to bind to HLA-A2.1 gene-transfected L cells. These data suggested that peptides potentially recognized by cytotoxic T cells can bind to HLA class I molecules on tumor cells in vivo.

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  • REPRESSION OF INVOLUCRIN GENE-EXPRESSION BY TRANSCRIPTIONAL ENHANCER FACTOR 1 (TEF-1)

    H TAKAHASHI, H KOBAYASHI, S MATSUO, H IIZUKA

    ARCHIVES OF DERMATOLOGICAL RESEARCH   287 ( 8 )   740 - 746   1995.10

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    Involucrin is one of the precursor proteins of keratinocyte cornified envelope that is formed beneath the inner surface of the cell membrane during terminal differentiation. Although involucrin is specifically expressed in the upper squamous cells of the epidermis, the precise regulatory mechanism of involucrin gene expression remains unknown. Transcriptional enhancer factor 1 (TEF-1), which binds to SV40 enhancer, is a nuclear protein expressed in various types of cells including keratinocytes. Immunohistochemical study has revealed that TEF-1 protein is highly expressed on the basal cell layer of the epidermis. To examine the possible regulatory mechanism of involucrin gene expression by TEF-1 protein, we analysed involucrin promoter activity of the INV-CAT vector, which was constructed by connecting the 5' upstream region of the involucrin gene (-801 bp upstream from the transcription start site and downstream including the untranslated first exon) to the chloramphenicol acetyltransferase (CAT) reporter gene. The INV-CAT vector was transfected to SV30-transformed human keratinocytes (SVHK). Cotransfection of the TEF-1 expression vector significantly repressed INV-CAT promoter activity in a dose-dependent manner. The repression was also observed by transfection of the GAL4-TEF-1 vector, which was constructed by replacement of the TEF-1 DNA binding domain by the GAL4 activator domain. This suggests that TEF-1-induced repression is due to interference/squelching of a limiting transcriptional intermediary factor that is essential for involucrin expression. Analysis of the deleted INV-CAT vector suggested that the region from -599 to -495 of the involucrin gene, which contains two possible TEF-1 binding sites, was critical for the repression of the involucrin gene by TEF-1. By gel retardation analysis, the specific DNA binding of SVHK cell nuclear extracts and the recombinant TEF-1 protein was confirmed. TEF-1-dependent repression of involucrin gene expression might explain the suprabasal involucrin expression in the epidermis.

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  • NATURALLY PROCESSED HLA-DR9/DR53 (DRB1-ASTERISK-0901/DRB4-ASTERISK-0101)-BOUND PEPTIDES

    G FUTAKI, H KOBAYASHI, K SATO, M TANEICHI, M KATAGIRI

    IMMUNOGENETICS   42 ( 4 )   299 - 301   1995.8

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  • PEPTIDE MOTIFS OF HLA-DR4/DR53 (ORB1(ASTERISK)0405/DRB4(ASTERISK)0101) MOLECULES

    R KINOUCHI, H KOBAYASI, K SATO, S KIMURA, M KATAGIRI

    IMMUNOGENETICS   40 ( 5 )   376 - 378   1994.9

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    DOI： 10.1007/BF01246679

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Presentations

  • 節外性NK/T細胞リンパ腫、鼻型における可溶性CD27の発現

    長門利純, 小松田浩樹, 林 隆介, 高原 幹, 岸部 幹, 小坂 朱, 大栗敬幸, 及川賢輔, 河野通久, 山木英聖, 脇坂理紗, 大原賢三, 熊井琢美, 片田彰博, 原渕保明, 小林博也

    第82回 日本癌学会学術総会 

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    Event date： 2023.9

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  • コルヒチン腫瘍内投与の腫瘍血管破綻により誘導される単球由来樹状細胞の性状解析

    小坂 朱, 安田俊輔, 大栗敬幸, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第82回 日本癌学会学術総会 

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    Event date： 2023.9

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  • 頭頸部癌におけるPEG10を標的としたペプチドワクチン療法の開発

    小松田浩樹, 長門利純, 熊井琢美, 大原賢三, 山木英聖, 小坂 朱, 大栗敬幸, 小林博也

    第82回 日本癌学会学術総会 

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    Event date： 2023.9

    Language：English   Presentation type：Oral presentation (general)  

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  • HOXB7を標的としたペプチドワクチン療法

    小松田浩樹, 長門利純, 小林博也

    第56回 北海道病理談話会 

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    Event date： 2023.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • Nod様受容体とSTINGを標的とした腫瘍免疫療法の可能性評価

    大栗敬幸, 小坂 朱, 氏家菜々美, 小松田浩樹, 長門利純, 小林博也

    第56回 北海道病理談話会 

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    Event date： 2023.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 節外性NK/T細胞リンパ腫、鼻型における可溶性CD27の発現とバイオマーカーとしての可能性

    長門利純, 小松田浩樹, 小坂 朱, 大栗敬幸, 及川賢輔, 小林博也

    第27回 日本がん免疫学会総会 

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    Event date： 2023.7

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 腫瘍微小環境の炎症誘導により所属リンパ節に遊走する単球由来樹状細胞の性状解析

    大栗敬幸, 小坂 朱, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第27回 日本がん免疫学会総会 

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    Event date： 2023.7

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 担がんマウスの所属リンパ節におけるCD11b+Ly6Chigh単球由来樹状細胞の機能解析

    大栗敬幸, 小坂 朱, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第112回 日本病理学会総会 

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    Event date： 2023.4

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 上咽頭癌におけるCD74とMIFの発現

    長門利純, 小松田浩樹, 林 隆介, 安田俊輔, 小坂 朱, 大栗敬幸, 及川賢輔, 小林博也

    第112回 日本病理学会総会 

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    Event date： 2023.4

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  • 腫瘍微小環境におけるⅠ型IFN誘導アゴニストの比較

    小坂 朱, 大栗敬幸, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第112回 日本病理学会総会 

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    Event date： 2023.4

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  • SARS-CoV-2スパイク蛋白に対するヘルパーT細胞活性化ペプチドの同定と評価

    小林博也, 矢島優己, 小坂 朱, 長門利純, 廣橋良彦, 鳥越俊彦, 大栗敬幸

    第112回 日本病理学会総会 

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    Event date： 2023.4

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  • 口腔扁平上皮癌におけるFXYD3のバイオマーカーとしての意義をシグナル経路から検証する

    矢島優己, 大栗敬幸, 小坂 朱, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第81回 日本癌学会学術総会 

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    Event date： 2022.9 - 2022.10

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  • 頭頸部扁平上皮癌におけるPLAC1の発現およびPLAC1特異的ヘルパーT細胞の抗腫瘍効果に関する検討

    長門利純, 林 隆介, 熊井琢美, 大原賢三, 大栗敬幸, 野﨑 結, 原渕翔平, 小坂 朱, 矢島優己, 安田俊輔, 及川賢輔, 河野通久, 岸部 幹, 高原 幹, 原渕保明, 小林博也

    第81回 日本癌学会学術総会 

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    Event date： 2022.9 - 2022.10

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  • STINGアゴニストの腫瘍内投与後に所属リンパ節で増加する骨髄求系細胞の解析

    大栗敬幸, 小坂 朱, 矢島優己, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第81回 日本癌学会学術総会 

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    Event date： 2022.9 - 2022.10

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  • HOXB7を標的としたペプチドワクチン療法におけるMAPK阻害の併用効果の検討

    小松田浩樹, 熊井琢美, 大原賢三, 長門利純, 小坂 朱, 大栗敬幸, 小林博也

    第81回 日本癌学会学術総会 

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    Event date： 2022.9 - 2022.10

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  • コルヒチンの腫瘍内投与はⅠ型インターフェロンによる抗腫瘍免疫を誘導する

    安田俊輔, 小松田浩樹, 矢島優己, 小坂 朱, 長門利純, 大栗敬幸, 及川賢輔, 北田正博, 小林博也

    第81回 日本癌学会学術総会 

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    Event date： 2022.9 - 2022.10

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  • 腫瘍微小環境におけるⅠ型IFN誘導能の検討

    小坂 朱, 大栗敬幸, 矢島優己, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第81回 日本癌学会学術総会 

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    Event date： 2022.9 - 2022.10

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  • STINGアゴニストの腫瘍内投与後に所属リンパ節で増加する骨髄球系細胞の解析

    大栗敬幸, 小坂 朱, 矢島優己, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第55回 北海道病理談話会 

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    Event date： 2022.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 微小管阻害薬の作用の違いによる抗腫瘍効果のメカニズムおよび抗腫瘍免疫応答の比較検討

    安田俊輔, 小松田浩樹, 矢島優己, 小坂 朱, 長門利純, 大栗敬幸, 及川賢輔, 小林博也

    第55回 北海道病理談話会 

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    Event date： 2022.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 頭頸部癌におけるPEG10の発現およびPEG10特異的ヘルパーT細胞の抗腫瘍効果に関する検討

    長門利純, 小松田浩樹, 安田俊輔, 矢島優己, 小坂 朱, 大栗敬幸, 及川賢輔, 原渕保明, 小林博也

    第55回 北海道病理談話会 

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    Event date： 2022.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • SARS-CoV2に対するヘルパーT細胞活性化ペプチドワクチンの開発研究

    矢島優己, 大栗敬幸, 小坂 朱, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 廣橋良彦, 鳥越俊彦, 小林博也

    第55回 北海道病理談話会 

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    Event date： 2022.9

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  • コルヒチンの腫瘍血管破壊による抗腫瘍免疫応答の誘導

    安田俊輔, 大栗敬幸, 矢島優己, 小松田浩樹, 小坂 朱, 長門利純, 及川賢輔, 小林博也

    第26回 日本がん免疫学会総会 

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    Event date： 2022.7

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  • マウス扁平上皮癌モデルを用いたバイオマーカーとしてのFXYD3の有用性の評価

    矢島優己, 大栗敬幸, 小坂 朱, 安田俊輔, 永田真莉乃, 小松田浩樹, 長門利純, 及川賢輔, 竹川政範, 小林博也

    第111回 日本病理学会総会 

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    Event date： 2022.4

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  • cGAMPの腫瘍内投与後に所属リンパ節で認められるCD11bmidLy6Chigh細胞の解析

    大栗敬幸, 小坂 朱, 矢島優己, 安田俊輔, 永田真莉乃, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第111回 日本病理学会総会 

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    Event date： 2022.4

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 頭頸部癌におけるPEG10を標的としたペプチドワクチン療法の開発

    小松田浩樹, 長門利純, 河野通久, 山木英聖, 脇坂理紗, 熊井琢美, 岸部 幹, 高原 幹, 片田彰博, 林 達哉, 小林博也, 原渕保明

    第2回 日本耳鼻咽喉科免疫アレルギー感染症学会 

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    Event date： 2022.4

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • コルヒチン腫瘍内投与によるⅠ型IFNを介した抗腫瘍免疫についての検討

    安田俊輔, 小松田浩樹, 矢島優己, 永田真莉乃, 小坂 朱, 長門利純, 大栗敬幸, 及川賢輔, 小林博也

    第111回 日本病理学会総会 

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    Event date： 2022.4

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  • CD47発現は乳がん組織におけるCD8+およびCD68陽性細胞の浸潤と正に相関する

    小坂 朱, 大栗敬幸, 矢島優己, 安田俊輔, 小松田浩樹, 永田真莉乃, 長門利純, 及川賢輔, 小林博也

    第111回 日本病理学会総会 

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    Event date： 2022.4

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  • 頭頸部癌に対するPEG10を標的としたヘルパーペプチドワクチンの基礎的解析

    長門利純, 小松田浩樹, 安田俊輔, 矢島優己, 永田真莉乃, 小坂 朱, 大栗敬幸, 及川賢輔, 原渕保明, 小林博也

    第111回 日本病理学会総会 

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    Event date： 2022.4

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  • NCOA4-RET融合遺伝子が確認された唾液腺導管内癌の一例

    山口朋美, 橋場なつみ, 濱田 誠, 坂東伸幸, 及川賢輔, 小林博也, 武井英博

    第60回 日本臨床細胞学会秋期大会 

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    Event date： 2021.11

    Language：Japanese   Presentation type：Poster presentation  

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  • SPESP1はエピジェネティックに発現抑制を受けるステルスがん抗原としてがん免疫の標的抗原になりうる

    大栗敬幸, 小坂 朱, 矢島優己, 永田真莉乃, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 小林博也

    第80回 日本癌学会学術総会 

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    Event date： 2021.9 - 2021.10

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  • Combined treatment with celecoxib improves antitumor efficacy of STING agonists

    小坂 朱, 大栗敬幸, 矢島優己, 安田俊輔, 小松田浩樹, 永田真莉乃, 長門利純, 及川賢輔, 小林博也

    第80回 日本癌学会学術総会 

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    Event date： 2021.9 - 2021.10

    Language：English   Presentation type：Oral presentation (general)  

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  • 続報）コルヒチン腫瘍内投与による抗腫瘍効果と免疫学的機構に関する検討

    安田俊輔, 大栗敬幸, 矢島優己, 永田真莉乃, 小松田浩樹, 小坂 朱, 長門利純, 及川賢輔, 田中宏樹, 西川祐司, 北田正博, 小林博也

    第54回 北海道病理談話会 

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    Event date： 2021.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • セルレイン誘発急性膵炎マウスモデルを用いた新たな膵炎治療法の開発

    矢島優己, 大栗敬幸, 小坂 朱, 永田真莉乃, 安田俊輔, 小松田浩樹, 長門利純, 及川賢輔, 竹川政範, 小林博也

    第54回 北海道病理談話会 

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    Event date： 2021.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • エピジェネティックに発現抑制を受けるステルスがん抗原SPESP1を標的とした新しいがん免疫療法の開発

    大栗敬幸, 小坂朱, 矢島優己, 永田真莉乃, 安田俊輔, 長門利純, 及川賢輔, 小林博也

    第25回 日本がん免疫学会総会 

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    Event date： 2021.7

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  • 頭頸部扁平上皮癌におけるplacenta-specific 1（PLAC1）の発現とPLAC1特異的ヘルパーT細胞における抗腫瘍効果の検討

    長門利純, 林 隆介, 熊井琢美, 大原賢三, 野﨑 結, 原渕翔平, 河野通久, 山木英聖, 岸部 幹, 高原 幹, 片田彰博, 林 達哉, 原渕保明, 小林博也

    第1回 日本耳鼻咽喉科免疫アレルギー感染症学会 

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    Event date： 2021.6 - 2021.7

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 上咽頭癌におけるCD70およびCD27の発現解析

    長門利純, 林 隆介, 永田真莉乃, 矢島優己, 安田俊輔, 小坂 朱, 大栗敬幸, 及川賢輔, 原渕保明, 小林博也

    第110回 日本病理学会総会 

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    Event date： 2021.4

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  • マウスモデルを用いた扁平上皮癌に対するレンバチニブの有用性の評価

    矢島優己, 大栗敬幸, 小坂 朱, 安田俊輔, 永田真莉乃, 林 隆介, 長門利純, 及川賢輔, 竹川政範, 小林博也

    第110回 日本病理学会総会 

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    Event date： 2021.4

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  • コルヒチン腫瘍内投与による抗腫瘍効果と免疫学的機構に関する検討

    安田俊輔, 大栗敬幸, 小坂 朱, 永田真莉乃, 林 隆介, 矢島優己, 長門利純, 及川賢輔, 小林博也

    第110回 日本病理学会総会 

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    Event date： 2021.4

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  • Epigenetically silenced antigens in tumor cells would be suitable targets for cancer immunotherapy

    小坂 朱, 大栗敬幸, 矢島優巳, 安田俊輔, 永田真莉乃, 長門利純, 及川賢輔, 小林博也

    第110回 日本病理学会総会 

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    Event date： 2021.4

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  • 呼吸不全の加療中に突然死亡しCOVI-19が疑われた１剖検例

    永田真莉乃, 長門利純, 梅影泰寛, 安田俊輔, 矢島優己, 小坂 朱, 大栗敬幸, 及川賢輔, 樋田京子, 小林博也

    第110回 日本病理学会総会 

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    Event date： 2021.4

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  • 乳がん組織におけるマクロファージとCD47―新しいがん免疫治療法の糸口

    大栗敬幸, 小坂 朱, 石橋 佳, 長門利純, 小林博也

    第110回 日本病理学会総会 

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    Event date： 2021.4

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • マウス扁平上皮癌に対するレンバチニブ及び免疫チェックポイント阻害薬の治療効果の検討

    矢島優己, 大栗敬幸, 小坂 朱, 林 隆介, 永田真莉乃, 安田俊輔, 長門利純, 及川賢輔, 竹川政範, 小林博也

    第53回 北海道病理談話会 

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    Event date： 2020.10

    Language：Japanese  

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  • 上咽頭癌におけるCD70およびCD27の発現解析

    長門利純, 林 隆介, 永田真莉乃, 矢島優己, 安田俊輔, 小坂 朱, 大栗敬幸, 及川賢輔, 原渕保明, 小林博也

    第53回 北海道病理談話会 

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    Event date： 2020.10

    Language：Japanese  

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  • 腫瘍組織内のSTING活性化により腫瘍内に浸潤する好中球は抗腫瘍免疫応答を促進する

    永田真莉乃, 大栗敬幸, 小坂朱, 矢島優己, 原渕翔平, 林隆介, 長門利純, 及川賢輔, 小林博也

    第53回 北海道病理談話会 

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    Event date： 2020.10

    Language：Japanese  

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  • リン酸化ビメンチンを標的抗原とした転移性大腸癌に対する免疫療法

    大原賢三, 熊井琢美, 長門利純, 林 隆介, 矢島優己, 大栗敬幸, 小林博也

    第24回 日本がん免疫学会総会 

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    Event date： 2020.10

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  • 腫瘍内へのcGAMPと抗CD47抗体の同時投与は腫瘍内マクロファージの活性化を介して抗腫瘍免疫を増強する

    大栗敬幸, 小坂 朱, 石橋 佳, 長門利純, 原渕翔平, 永田真莉乃, 林 隆介, 矢島優己, 及川賢輔, 小林博也

    第２４回日本がん免疫学会総会 

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    Event date： 2020.10

    Language：Japanese  

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  • 上咽頭癌におけるCD70およびCD27の発現解析

    長門利純, 林 隆介, 原渕翔平, 永田真莉乃, 矢島優己, 小坂 朱, 大栗敬幸, 野﨑 結, 大原賢三, 熊井琢美, 岸部 幹, 高原 幹, 及川賢輔, 原渕保明, 小林博也

    第24回 日本がん免疫学会総会 

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    Event date： 2020.10

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  • マウス扁平上皮癌に対するレンバチニブと免疫チェックポイント阻害薬の併用治療は腫瘍増殖効果を示す

    矢島優己, 大栗敬幸, 小坂 朱, 原渕翔平, 永田真莉乃, 林 隆介, 長門利純, 熊井琢美, 及川賢輔, 竹川政範, 小林博也

    第24回 日本がん免疫学会総会 

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    Event date： 2020.10

    Language：Japanese  

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  • 腫瘍組織内のSTING刺激でCXCR2依存的に腫瘍内浸潤する好中球はI型IFNにより活性化され抗腫瘍免疫応答を作動させる

    永田真莉乃, 大栗敬幸, 小坂朱, 矢島優己, 原渕翔平, 林隆介, 長門利純, 及川賢輔, 小林博也

    第24回 日本がん免疫学会総会 

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    Event date： 2020.10

    Language：Japanese  

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  • 頭頸部悪性腫瘍におけるCD74とMIFの発現

    林 隆介, 長門利純, 原渕翔平, 熊井琢美, 岸部 幹, 高原 幹, 小林博也, 原渕保明

    第38回 日本耳鼻咽喉科免疫アレルギー学会 

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    Event date： 2020.9

    Language：Japanese  

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  • マクロファージのSTING依存的腫瘍内浸潤による抗腫瘍免疫応答の増強効果

    大栗敬幸, 小坂朱, 石橋佳, 長門利純, 小林博也

    第93回 日本生化学会大会 

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    Event date： 2020.9

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • 頭頸部扁平上皮癌におけるPLAC1の発現とPLAC1特異的T細胞による抗腫瘍効果の検討

    林 隆介, 長門利純, 熊井琢美, 河野通久, 岸部 幹, 高原 幹, 片田彰博, 林 達哉, 小林博也, 原渕保明

    第44回 日本頭頸部癌学会 

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    Event date： 2020.7

    Language：Japanese  

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  • STINGの活性化に伴う好中球の腫瘍内浸潤は抗腫瘍免疫応答を促進させる

    永田真莉乃, 大栗敬幸, 小坂朱, 矢島優己, 原渕翔平, 林隆介, 長門利純, 及川賢輔, 小林博也

    第109回 日本病理学会総会 

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    Event date： 2020.7

    Language：Japanese  

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  • 唾液腺分泌癌の3例

    長門利純, 及川賢輔, 永田真莉乃, 大内知之, 片岡俊朗, 加藤生真, 西原弘治, 佐藤啓介, 大栗敬幸, 小林博也

    第109回 日本病理学会総会 

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    Event date： 2020.7

    Language：Japanese  

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  • がんのエピジェネティック変異を標的としたがん免疫治療法の確立．

    大栗敬幸, 小坂 朱, 矢島優己, 原渕翔平, 永田真莉乃, 林 隆介, 長門利純, 及川賢輔, 小林博也

    第１０９回日本病理学会総会 

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    Event date： 2020.7

    Language：Japanese  

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  • Placenta-specific protein 1特異的T細胞の誘導とその抗腫瘍効果の検討

    林 隆介, 長門利純, 熊井琢美, 永田真莉乃, 原渕翔平, 矢島優己, 小坂 朱, 大栗敬幸, 及川賢輔, 原渕保明, 小林博也

    第109回 日本病理学会総会 

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    Event date： 2020.7

    Language：Japanese  

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  • 扁平上皮癌に対するレンバチニブと免疫治療の併用による治療効果を検討し、口腔癌治療への応用を考える

    矢島優己, 大栗敬幸, 小坂 朱, 原渕翔平, 永田真莉乃, 林 隆介, 長門利純, 及川賢輔, 竹川政範, 小林博也

    第109回 日本病理学会総会 

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    Event date： 2020.7

    Language：Japanese  

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  • 抗腫瘍免疫応答におけるIRF3の役割について

    小坂 朱, 大栗敬幸, 永田真莉乃, 原渕翔平, 林 隆介, 矢島優己, 長門利純, 及川賢輔, 小林博也

    第109回 日本病理学会総会 

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    Event date： 2020.7

    Language：Japanese  

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  • Placenta-specific protein 1特異的T細胞の誘導とその抗腫瘍効果の検討

    林 隆介, 長門利純, 熊井琢美, 永田真莉乃, 原渕翔平, 矢島優己, 小坂 朱, 大栗敬幸, 及川賢輔, 岸部 幹, 高原 幹, 原渕保明, 小林博也

    第46回 北海道頭頸部腫瘍研究会 

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    Event date： 2020.2

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • がんの免疫逃避機構を利用したがん免疫治療法に関する基盤研究

    大栗敬幸, 小 坂朱, 原渕翔平, 永田真莉乃, 林 隆介, 矢島優己, 長門利純, 及川賢輔, 小林博也

    第52回 北海道病理談話会 

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    Event date： 2019.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：旭川市  

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  • Placenta-specific protein 1を標的としたペプチドワクチン療法の検討

    林 隆介, 長門利純, 熊井琢美, 永田真莉乃, 原渕翔平, 矢島優己, 小坂 朱, 大栗敬幸, 及川賢輔, 原渕保明, 小林博也

    第52回 北海道病理談話会 

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    Event date： 2019.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • STINGアゴニストcGAMP とCOX-2阻害薬celecoxibの併用による抗腫瘍効果

    小坂 朱, 大栗敬幸, 永田真莉乃, 原渕翔平, 林 隆介, 矢島優己, 長門利純, 及川賢輔, 小林博也

    第52回 北海道病理談話会 

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    Event date： 2019.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：旭川市  

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  • STING活性化療法とシスプラチン療法の併用に関する基礎研究

    原渕翔平, 大栗敬幸, 小坂 朱, 永田真莉乃, 林 隆介, 矢島優己, 平田 結, 大原賢三, 熊井琢美, 長門利純, 及川賢輔, 小林博也, 原渕保明

    第52回 北海道病理談話会 

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    Event date： 2019.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：旭川市  

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  • Expression of cell surface CD74 and macrophage migration inhibitory factor in malignant tumors of head and neck region.

    林 隆介, 長門利純, 熊井琢美, 永田真莉乃, 原渕翔平, 矢島優己, 小坂 朱, 大栗敬幸, 及川賢輔, 岸部 幹, 高原 幹, 原渕保明, 小林博也

    第78回 日本癌学会学術総会 

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    Event date： 2019.9

    Language：English   Presentation type：Poster presentation  

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  • Combined administration of cGAMP and celecoxib enhances antitumor efficacy through T-cells and STING signaling.

    小坂 朱, 大栗敬幸, 永田真莉乃, 原渕翔平, 林 隆介, 矢島優己, 長門利純, 及川賢輔, 小林博也

    第78回 日本癌学会学術総会 

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    Event date： 2019.9

    Language：English   Presentation type：Poster presentation  

    Venue：京都市  

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  • シスプラチンとSTINGアゴニストの併用療法は相乗的な抗腫瘍効果を示す

    原渕翔平, 大栗敬幸, 小坂 朱, 永田真莉乃, 林 隆介, 矢島優己, 平田 結, 大原賢三, 熊井琢美, 長門利純, 及川賢輔, 原渕保明, 小林博也

    第78回 日本癌学会学術総会 

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    Event date： 2019.9

    Language：Japanese   Presentation type：Poster presentation  

    Venue：京都市  

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  • A novel cancer immunotherapy targeting “epigenetically silenced tumor antigens”

    Ohkuri T., Kosaka A., Harabuchi S., Nagata M., Hayashi R., Yajima Y., Nagato T., Oikawa K., Kobayashi H.

    第78回 日本癌学会学術総会 

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    Event date： 2019.9

    Language：English   Presentation type：Oral presentation (general)  

    Venue：京都市  

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  • Expression of CD27 and its soluble form in nasal natural killer/T-cell lymphoma.

    Nagato T., Hayashi R., Harabuchi S., Kumai T., Kishibe K., Takahara M., Nagata M., Yajima Y., Kosaka A., Ohkuri T., Oikawa K., Harabuchi Y., Kobayashi, H.

    第78回 日本癌学会学術総会 

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    Event date： 2019.9

    Language：English   Presentation type：Poster presentation  

    Venue：京都市  

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  • マクロファージを介したcGAMPと抗CD40抗体との併用による抗腫瘍効果

    永田真莉乃, 大栗敬幸, 小坂 朱, 原渕翔平, 林隆介, 矢島優己, 長門利純, 及川賢輔, 原渕保明, 小林博也

    第78回 日本癌学会学術総会 

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    Event date： 2019.9

    Language：Japanese   Presentation type：Poster presentation  

    Venue：京都市  

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  • がん特異的な翻訳後修飾を受けたp53タンパク質は特異的T細胞応答を惹起する

    大原賢三, 大栗敬幸, 長門利純, 小林博也

    第23回 日本がん免疫学会総会 

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    Event date： 2019.8

    Language：Japanese   Presentation type：Poster presentation  

    Venue：高知市  

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  • DNAメチル基転移酵素阻害剤によってがん細胞に再発現される『ステルスがん抗原』はがん免疫治療の標的抗原として有用である

    大栗敬幸, 小坂 朱, 長門利純, 小林博也

    第23回 日本がん免疫学会総会 

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    Event date： 2019.8

    Language：Japanese   Presentation type：Poster presentation  

    Venue：高知市  

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  • 新たな癌抗原ペプチドとしての翻訳後修飾タンパク質の可能性

    小林博也

    第１１９回 北海道癌談話会春期シンポジウム 

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    Event date： 2019.6

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

    Venue：札幌市  

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  • リン酸化ビメンチンを標的とした免疫療法の基礎的解析

    大原賢三, 大原みずほ, 長門利純, 大栗敬幸, 小坂 朱, 林 隆介, 永田真莉乃, 原渕翔平, 及川賢輔, 小林博也

    第108回 日本病理学会総会 

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    Event date： 2019.5

    Language：Japanese   Presentation type：Poster presentation  

    Venue：東京  

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  • cGAMPによるSTING依存的な免疫活性化型好中球の腫瘍内浸潤メカニズムの解明

    大栗敬幸, 小坂 朱, 石橋 佳, 永田真莉乃, 原渕翔平, 林 隆介, 長門利純, 及川賢輔, 青木直子, 小林博也

    第108回 日本病理学会総会 

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    Event date： 2019.5

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：東京  

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  • 鼻性NK/T細胞リンパ腫におけるCD27の発現

    長門利純, 林 隆介, 原渕翔平, 永田真莉乃, 大原賢三, 大原みずほ, 小坂 朱, 大栗敬幸, 及川賢輔, 小林博也

    第108回 日本病理学会総会 

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    Event date： 2019.5

    Language：Japanese   Presentation type：Poster presentation  

    Venue：東京  

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  • Combined a STING ligand cGAMP and the COX-2 inhibitor celecoxib induces antitumor responses.

    小坂 朱, 大栗敬幸, 永田真莉乃, 原渕翔平, 林 隆介, 長門利純, 及川賢輔, 青木直子, 小林博也

    第108回 日本病理学会総会 

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    Event date： 2019.5

    Language：Japanese   Presentation type：Poster presentation  

    Venue：東京  

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  • 頭頸部悪性腫瘍におけるCD74の発現

    林 隆介, 長門利純, 永田真莉乃, 原渕翔平, 大原賢三, 大原みずほ, 小坂 朱, 大栗敬幸, 及川賢輔, 小林博也

    第108回 日本病理学会総会 

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    Event date： 2019.5

    Language：Japanese   Presentation type：Poster presentation  

    Venue：東京  

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  • マクロファージを介したcGAMPと抗CD40抗体との併用による抗腫瘍効果

    永田真莉乃, 小坂 朱, 大栗敬幸, 原渕翔平, 林隆介, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第108回 日本病理学会総会 

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    Event date： 2019.5

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：東京  

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  • マウス扁平上皮癌モデルを用いた、化学療法とSTING活性化療法の併用に関する基礎研究

    原渕翔平, 大栗敬幸, 小坂 朱, 永田真莉乃, 林 隆介, 大原賢三, 大原みずほ, 長門利純, 及川賢輔, 小林博也

    第108回 日本病理学会総会 

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    Event date： 2019.5

    Language：Japanese   Presentation type：Poster presentation  

    Venue：東京  

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  • ストレス存在下に翻訳後修飾を受けた免疫原性を有するp53を標的としたヘルパーペプチドワクチン療法の解析

    大原賢三, 小林博也

    第13回臨床ストレス応答学会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 鼻性NK/T細胞リンパ腫における免疫抑制機構の解明と新規免疫療法の開発

    長門利純, 原渕保明, 小林博也

    第107回日本病理学会総会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • リン酸化抗原を特異的に認識するT細胞の抗腫瘍効果の解析

    大原賢三, 大原みずほ, 長門利純, 大栗敬幸, 小坂朱, 林隆介, 原渕翔平, 永田真莉乃, 及川賢輔, 青木直子, 小林博也

    第98回 北海道医学大会 病理分科会・第51回 北海道病理談話会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 2’3’-cGAMP とcelecoxibの併用治療による抗腫瘍効果の誘導

    小坂朱, 大栗敬幸, 大原賢三, 永田真莉乃, 原渕翔平, 大原みずほ, 林隆介, 長門利純, 及川賢輔, 青木直子, 原渕保明, 小林博也

    第98回 北海道医学大会 病理分科会・第51回 北海道病理談話会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • STINGを介した炎症反応の惹起とがん免疫治療への応用

    大栗敬幸, 小林博也, 小坂朱

    第98回 北海道医学大会 病理分科会・第51回 北海道病理談話会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • 鼻性NK/T細胞リンパ腫におけるCDK1とサバイビンの発現

    長門利純, 大原賢三, 原渕翔平, 林 隆介, 大栗敬幸, 永田真莉乃, 大原みずほ, 小坂 朱, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第51回北海道病理談話会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 免疫チェックポイント分子PD－L１特異的CD４陽性ヘルパーT細胞クローンの樹立とその抗腫瘍効果

    野崎 結, 大原賢三, 永田 真莉乃, 原渕翔平, 長門利純, 小坂 朱, 大栗敬幸, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第１１８回北海道癌談話会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 腫瘍免疫の基礎・がん免疫サイクルを回すには

    大栗敬幸, 上原治朗, 小林博也

    第82回 日本皮膚科学会東部支部学術大会 

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    Event date： 2018.10

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • Establishment and characterization of murine breast cancer cell line with highly lung metastatic potential

    永田真莉乃, 大栗敬幸, 小坂朱, 原渕翔平, 平田結, 大原賢三, 長門利純, 青木直子, 及川賢輔, 小林博也

    第77回日本癌学会学術総会 

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    Event date： 2018.9

    Language：English   Presentation type：Poster presentation  

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  • Combination of a STING ligand cGAMP and the COX-2 inhibitor celecoxib induces antitumor effects

    小坂朱, 大栗敬幸, 大原賢三, 永田真莉乃, 原渕翔平, 大原みずほ, 林隆介, 長門利純, 及川賢輔, 青木直子, 原渕保明, 小林博也

    第77回 日本癌学会学術総会 

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    Event date： 2018.9

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  • Spontaneous immune responses in breast cancer patients against TWIST1: potential as a highly immunogenic shared antigen

    大栗敬幸, 小坂朱, 石橋佳, 永田真莉乃, 原渕翔平, 大原賢三, 野崎結, 大原みずほ, 林隆介, 長門利純, 及川賢輔, 青木直子, 小林博也

    第77回 日本癌学会学術総会 

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    Event date： 2018.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • がん転移関連分子TWIST1は乳がん患者において強い免疫原性を示し、標的抗原として有望ながん抗原となりうる

    大栗敬幸, 石橋佳, 小坂朱, 永田真莉乃, 原渕翔平, 大原賢三, 大原みずほ, 長門利純, 及川賢輔, 青木直子, 小林博也

    第22回 がん免疫学会総会 

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    Event date： 2018.8

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • Expression of programmed death-ligand 1 in nasal natural killer/T-cell lymphoma. International conference

    Nagato T., Ohkuri T., Ohara K., Hirata-Nozaki Y., Kishibe K., Takahara M., Kumai T., Araki D., Komatsuda H., Kobayashi H., Harabuchi Y.

    18th International conference on EBV & KSHV 

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    Event date： 2018.7

    Language：English   Presentation type：Poster presentation  

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  • 鼻性NK/T細胞リンパ腫におけるCD27の発現

    長門利純, 林 隆介, 原渕翔平, 野崎 結, 大原賢三, 熊井琢美, 岸部 幹, 高原 幹, 永田真莉乃, 大原みずほ, 大栗敬幸, 小坂 朱, 青木直子, 及川賢輔, 小林博也, 原渕保明

    第15回EBウイルス研究会 

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    Event date： 2018.7

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 高肺転移能をもつマウス乳癌細胞株の樹立とその性状解析

    永田真莉乃, 大栗敬幸, 小坂朱, 原渕翔平, 大原賢三, 大原みずほ, 長門利純, 青木直子, 及川賢輔, 小林博也

    第107回日本病理学会総会 

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    Event date： 2018.6

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  • 高分化乳頭状中皮腫様の増生パターンをとった悪性中皮腫の一例

    青木直子, 岩崎沙理, 永田真莉乃, 長門利純, 小坂朱, 大栗敬幸, 及川賢輔, 武井英博, 小林博也

    第107回 日本病理学会総会 

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    Event date： 2018.6

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  • Influence of cisplatin on cancer immunotherapy in murine squamous cell carcinoma model

    原渕翔平, 大栗敬幸, 永田真莉乃, 小坂朱, 林隆介, 大原みずほ, 大原賢三, 長門利純, 及川賢輔, 青木直子, 小林博也

    第107回 日本病理学会総会 

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    Event date： 2018.6

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  • 上皮間葉転換関連分子TWIST1を標的としたがん免疫治療法の開発研究

    大栗敬幸, 石橋佳, 小坂朱, 永田真莉乃, 原渕翔平, 大原賢三, 長門利純, 及川賢輔, 青木直子, 小林博也

    第107回 日本病理学会総会 

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    Event date： 2018.6

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  • 腫瘍組織における抗原提示細胞の役割とその重要性-免疫抑制環境の再起動

    大栗敬幸, 小坂朱, 長門利純, 小林博也

    第107回 日本病理学会総会 

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    Event date： 2018.6

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • cGAMPと抗CD47抗体の腫瘍内併用投与は抗腫瘍効果を増強する

    小坂朱, 大栗敬幸, 石橋佳, 大原賢三, 永田真莉乃, 原渕翔平, 長門利純, 及川賢輔, 青木直子, 小林博也

    第107回 日本病理学会総会 

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    Event date： 2018.6

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  • リン酸化抗原を標的としたヘルパーペプチドワクチン療法の基礎的解析

    大原賢三, 大原みずほ, 長門利純, 大栗敬幸, 小坂朱, 永田真莉乃, 青木直子, 及川賢輔, 小林博也

    第107回 日本病理学会総会 

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    Event date： 2018.6

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  • Targeting phosphorylated p53 to elicit tumor-reactive T helper responses agaist head and neck squamous cell carcinoma International conference

    Kenzo Ohara, Takumi Kumai, Toshihiro Nagato, Takayuki Ohkuri, Yui Nozaki, Mizuho Ohara, Nobuyuki Bandoh, Tatsuya Hayashi, Yasuaki Harabuchi, Hiroya Kobayashi

    米国癌学会総会 

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    Event date： 2018.4

    Language：English   Presentation type：Poster presentation  

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  • 翻訳後修飾を受けたリン酸化p53を標的としたペプチドワクチン療法の検討

    大原賢三, 野﨑結, 熊井琢美, 長門利純, 原渕翔平, 小林博也, 原渕保明

    第36回 日本耳鼻咽喉科免疫アレルギー学会 

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    Event date： 2018.2

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 鼻性NK/T細胞リンパ腫におけるCDK1とサバイビンの発現

    長門利純, 上田征吾, 熊井琢美, 駒林優樹, 岸部 幹, 高原 幹, 小林博也, 原渕保明

    第65回日本ウイルス学会学術集会 

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    Event date： 2017.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 鼻性NK/T細胞リンパ腫におけるPD-L1の発現

    長門利純, 大栗敬幸, 大原賢三, 野﨑 結, 永田真莉乃, 原渕翔平, 小坂 朱, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第50回北海道病理談話会 

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    Event date： 2017.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 腫瘍環境のマクロファージを介したcGAMPと抗CD47抗体との併用による抗腫瘍効果

    小坂朱, 大栗敬幸, 石橋佳, 大原賢三, 平田結, 永田真莉乃, 原渕翔平, 長門利純, 及川賢輔, 青木直子, 小林博也

    第50回 北海道病理談話会 

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    Event date： 2017.10

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  • NF-kB/TLR4を介したSTING刺激によるM1マクロファージの腫瘍内集積

    大栗敬幸, 小坂朱, 石橋佳, 大原賢三, 平田結, 及川賢輔, 青木直子, 長門利純, 永田真莉乃, 原渕翔平, 小林博也

    第50回 北海道病理談話会 

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    Event date： 2017.10

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  • Induction of tumor-reactive T helper-cell responses by phospho-peptide epitopes from tumor protein p53

    大原賢三, 平田結, 長門利純, 熊井琢美, 大栗敬幸, 青木直子, 原渕保明, 小林博也

    第75回日本癌学会学術総会 

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    Event date： 2017.9

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  • 鼻性NK/T細胞リンパ腫におけるCDK1とサバイビンの発現

    長門利純, 大原賢三, 平田 結, 原渕翔平, 永田真莉乃, 熊井琢美, 岸部 幹, 高原 幹, 大栗敬幸, 小坂 朱, 及川賢輔, 小林博也, 原渕保明

    第75回日本癌学会学術総会 

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    Event date： 2017.9

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  • Intratumoral coinjection of cGAMP with anti-CD47 mAb augments antitumor immunity mediated by macrophages in tumor sites

    小坂朱, 大栗敬幸, 石橋佳, 大原賢三, 平田結, 永田真莉乃, 原渕翔平, 長門利純, 及川賢輔, 青木直子, 原渕保明, 小林博也

    第75回 日本癌学会学術総会 

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    Event date： 2017.9

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  • 免疫チェックポイント分子PD-L1を標的としたCD4陽性ヘルパーT細胞クローンによる癌免疫療法

    平田 結, 大原賢三, 原渕翔平, 永田真莉乃, 大栗敬幸, 小坂 朱, 熊井琢美, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第75回日本癌学会学術総会 

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    Event date： 2017.9

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  • cGAMPの腫瘍内投与によってNF-kB/TLR4依存的にM1マクロファージを腫瘍内に集積させ抗腫瘍免疫を活性化させる

    大栗敬幸, 小坂朱, 石橋佳, 金城その子, 百合野秀朗, 大原賢三, 平田結, 及川賢輔, 青木直子, 長門利純, 池尾一穂, 橋本真一, 小林博也

    第75回 日本癌学会学術総会 

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    Event date： 2017.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 比較的まれな子宮頸部腫瘍の二例

    青木直子, 永田真莉乃, 長門利純, 小坂 朱, 大栗敬幸, 及川賢輔, 木村昭治, 佐藤啓介, 立野正敏, 小林博也

    第 180回 日本病理学会北海道支部学術集会(標本交見会) 

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    Event date： 2017.9

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  • 鼻性NK/T細胞リンパ腫におけるPD-L1の発現

    長門利純, 大栗敬幸, 大原賢三, 野崎 結, 熊井琢美, 上田征吾, 岸部 幹, 高原 幹, 小林博也, 原渕保明

    第14回EBウイルス研究会 

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    Event date： 2017.7

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • STINGリガンドの腫瘍内投与はNFkB/TLR4経路を介して腫瘍内にM1マクロファージを集積させる

    大栗敬幸, 小坂朱, 石橋佳, 金城その子, 熊井琢美, 大原賢三, 平田結, 永田真莉乃, 原渕翔平, 長門利純, 及川賢輔, 青木直子, 百合野秀朗, 門間則和, 池尾一穂, 橋本真一, 小林博也

    第21回 日本がん免疫学会総会 

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    Event date： 2017.6

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  • Intratumoral cGAMP injection recruits M1 macrophage in the tumor microenvironment via NF-kB/TLR4 pathway to trigger anti-tumor immunity International conference

    Takayuki Ohkuri, Akemi Kosaka, Takumi Kumai, Toshihiro Nagato, Kensuke Oikawa, Naoko Aoki, Hiroya Kobayashi

    36th Sapporo International Cancer Symposium 

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    Event date： 2017.6

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  • 鼻性NK/T細胞リンパ腫におけるPD-L1の発現

    長門利純, 大栗敬幸, 大原賢三, 平田 結, 熊井琢美, 小坂朱美, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第106回日本病理学会総会 

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    Event date： 2017.4

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  • STINGリガンドの腫瘍内投与は腫瘍内にマクロファージを集積させ抗腫瘍免疫応答を誘導する

    大栗敬幸, 小坂朱, 石橋佳, 熊井琢美, 大原賢三, 平田結, 長門利純, 及川賢輔, 青木直子, 小林博也

    第106回 日本病理学会総会 

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    Event date： 2017.4

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  • IFN-bとPD-L1阻害薬との併用治療によるメラノーマに対する抗腫瘍効果

    小坂朱, 上原治朗, 大栗敬幸, 大原賢三, 平田結, 長門利純, 永田真莉乃, 及川賢輔, 青木直子, 山本明美, 小林博也

    第106回 日本病理学会総会 

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    Event date： 2017.4

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  • 免疫チェックポイント分子PD-L1由来ペプチドによるCD4陽性ヘルパーT細胞クローンの樹立とその抗腫瘍効果

    平田 結, 大原賢三, 原渕翔平, 永田真莉乃, 大栗敬幸, 小坂 朱, 熊井琢美, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第106回日本病理学会総会 

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    Event date： 2017.4

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  • 翻訳後修飾を受けたリン酸化p53ペプチド特異的ヘルパーT細胞による抗腫瘍効果の解析

    大原賢三, 平田結, 熊井琢美, 大栗敬幸, 小坂朱, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第106回日本病理学会総会 

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    Event date： 2017.4

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  • 腫瘍免疫学•免疫治療学の進歩 S2-2:HLAクラスⅡ分子と癌抗原ヘルパーペプチド

    小林博也, 大栗敬幸, 長門利純, 大原賢三, 平田結, 石橋佳, 小坂朱, 熊井琢美, 青木直子

    第２５回日本組織適合性学会大会 

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    Event date： 2016.10

    Language：Japanese   Presentation type：Symposium, workshop panel (nominated)  

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  • メラノーマに対するPD-1/PD-L1阻害薬とIFN-βとの併用による抗腫瘍効果

    小坂朱, 上原治朗, 大栗敬幸, 石橋佳, 大原賢三, 平田結, 長門利純, 及川賢輔, 青木直子, 山本明美, 小林博也

    第96回 北海道医学大会 病理分科会・第49回 北海道病理談話会 

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    Event date： 2016.10

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  • STINGリガンドの腫瘍内投与はマクロファージを腫瘍内に集積させ抗腫瘍免疫応答を誘導する

    大栗敬幸, 小坂朱, 石橋佳, 熊井琢美, 平田結, 大原賢三, 永田真莉乃, 長門利純, 及川賢輔, 青木直子, 原渕保明, 小林博也

    第96回 北海道医学大会 病理分科会・第49回 北海道病理談話会、 

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    Event date： 2016.10

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  • 免疫チェックポイント分子PD-L1特異的CD４陽性ヘルパーT細胞クローンの樹立とその腫瘍応答性

    平田 結, 大原賢三, 大栗敬幸, 小坂 朱, 熊井琢美, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第96回 北海道医学大会 病理分科会・第49回 北海道病理談話会 

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    Event date： 2016.10

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  • Expression of programmed death-ligand 1 in nasal natural killer/T-cell lymphoma

    Nagato T., Ohkuri T., Ohara K., Hirata Y., Kishibe K., Ishibashi K., Kosaka A., Oikawa K., Kumai T., Takahara M., Harabuchi Y., Kobayashi H.

    第75回日本癌学会 

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    Event date： 2016.10

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  • STINGリガンドの腫瘍内投与は腫瘍内にマクロファージを集積させ抗腫瘍免疫応答を誘導する

    石橋桂, 大栗敬幸, 小坂朱, 熊井琢美, 平田結, 大原賢三, 長門利純, 及川賢輔, 青木直子, 原渕保明, 小林博也

    第75回日本癌学会学術総会 

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    Event date： 2016.10

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  • The immune checkpoint molecule, PD-L1 is a specific tumor associated antigen for CD4 helper T lymphocytes

    Hirata Y., Ohara K., Ohkuri T., Kosaka A., Ishibashi K., Kumai T., Nagato T., Aoki N., Oikawa K., Harabuchi Y., Kobayashi H.

    第75回日本癌学会学術総会 

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    Event date： 2016.10

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  • HER-3標的ヘルパーCD4 T細胞による抗腫瘍効果とHER阻害薬併用による相乗効果の検討

    熊井琢美, 大原賢三, 平田 結, 大栗敬幸, 小坂 朱, 長門利純, 石橋 佳, 及川賢輔, 原渕保明, 小林博也

    第75回日本癌学会学術総会 

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    Event date： 2016.10

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  • IFNβによるメラノーマからのケモカイン産生の誘導とPD-1/PD-L1阻害薬との併用による抗腫瘍効果

    小坂朱, 上原治朗, 大栗敬幸, 石橋佳, 大原賢三, 平田結, 長門利純, 及川賢輔, 青木直子, 山本明美, 小林博也

    第75回 日本癌学会学術総会 

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    Event date： 2016.10

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  • 2’3’-cGAMPの腫瘍内投与によって骨髄由来免疫抑制性細胞の腫瘍内浸潤を抑制する

    大栗敬幸, 小坂朱, 石橋佳, 大原賢三, 平田結, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第75回 日本癌学会学術総会 

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    Event date： 2016.10

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  • Induction of T helper-cell anti-tumor responses by phospho-peptide epitopes from tumor protein p53

    Ohara K., Hirata Y., Kumai T., Nagato T., Ishibashi K., Ohkuri T., Kosaka A., Oikawa K., Aoki N., Harabuchi Y., Kobayashi H.

    第75回日本癌学会 

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    Event date： 2016.10

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  • T細胞浸潤の少ないメラノーマに対する免疫チェックポイント阻害薬治療はIFNbの局所投与にて高い抗腫瘍効果を示す

    大栗敬幸, 上原治朗, 小坂朱, 石橋佳, 大原賢三, 平田結, 永田真莉乃, 長門利純, 熊井琢美, 及川賢輔, 青木直子, 山本明美, 小林博也

    第20回 日本がん免疫学会総会 

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    Event date： 2016.7

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  • 鼻性NK/T細胞リンパ腫におけるc-Metを標的とした免疫療法の開発

    熊井琢美, 大原賢三, 長門利純, 高原 幹, 片田彰博, 林 達哉, 小林博也, 原渕保明

    第117回日本耳鼻咽喉科学会総会 

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    Event date： 2016.5

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  • 免疫チェックポイント分子PD-L1由来ペプチドによるヘルパーT細胞クローンの樹立とその抗腫瘍効果

    平田 結, 大原賢三, 大栗敬幸, 小坂 朱, 熊井琢美, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第105回日本病理学会総会 

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    Event date： 2016.5

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  • HER-3由来CD4エピトープの同定およびHER阻害薬との併用について

    熊井琢美, 大原賢三, 石橋 佳, 大栗敬幸, 及川賢輔, 青木直子, 原渕保明, 小林博也

    第105回日本病理学会総会 

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    Event date： 2016.5

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  • 翻訳後修飾を受けたリン酸化p53ペプチド特異的ヘルパーT細胞による抗腫瘍効果の検討

    大原賢三, 平田 結, 大栗敬幸, 小坂 朱, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第105回日本病理学会総会 

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    Event date： 2016.5

    Language：Japanese   Presentation type：Poster presentation  

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  • STINGリガンドの腫瘍内投与における骨髄由来免疫抑制細胞に対する影響

    大栗敬幸, 小坂朱, 石橋佳, 大原賢三, 平田結, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第105回 日本病理学会総会 

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    Event date： 2016.5

    Language：Japanese   Presentation type：Poster presentation  

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  • Combination of a STING agonist and dexamethasone induces antitumor effects

    小坂朱, 大栗敬幸, 石橋佳, 大原賢三, 平田結, 長門利純, 及川賢輔, 青木直子, 原渕保明, 小林博也

    第105回 日本病理学会総会 

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    Event date： 2016.5

    Language：Japanese   Presentation type：Poster presentation  

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  • Neuropeptide signalings enhance cytokine production by antigen-specific T cells through activation of human dendritic cells.

    Hidemitsu Kitamura, Junya Ohtake, Shun Kaneumi, Mishie Tanino, Takuto, Kishikawa, Satoshi Terada, Kentaro Sumida, Kazutaka Masuko, Toshiyuki Kita, Sadahiro Iwabuchi, Shinya Tanaka, Hiroya Kobayashi

    第44回 日本免疫学会学術総会・学術集会 

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    Event date： 2015.11

    Language：English   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • Evaluating effects of 2'3'cGAMP on cancer metastasis in a mouse breast cancer model

    大栗敬幸, 石橋佳, 小坂朱, 大原賢三, 平田結, 青木直子, 及川賢輔, 小林博也

    第95回 北海道医学大会 病理分科会・第48回 北海道病理談話会 

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    Event date： 2015.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • HLA-Gを標的としたヘルパーT細胞を用いた免疫療法の検討

    石橋佳, 熊井琢美, 大栗敬幸, 大原賢三, 平田結, 小林博也

    第95回 北海道医学大会 病理分科会・第48回 北海道病理談話会 

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    Event date： 2015.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • セツキシマブの抗体依存性細胞障害活性に対するステロイドの影響

    長門利純, 熊井琢美, 平田結, 大原賢三, 石橋佳, 大栗敬幸, 小坂朱, 及川賢輔, 小林博也, 原渕保明

    第74回 日本癌学会学術総会 

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    Event date： 2015.10

    Language：Japanese   Presentation type：Poster presentation  

    Venue：名古屋市  

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  • EGFR阻害薬による抗腫瘍免疫への影響について

    熊井琢美, 大栗敬幸, 小坂朱, 長門利純, 石橋佳, 大原賢三, 平田結, 及川賢輔, 原渕保明, 小林博也

    第74回 日本癌学会学術総会 

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    Event date： 2015.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：名古屋市  

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  • HLA-Gエピトープを標的としたヘルパーT細胞の誘導と免疫療法の検討

    石橋佳, 熊井琢美, 大栗敬幸, 平田結, 大原賢三, 小林博也

    第74回 日本癌学会学術総会 

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    Event date： 2015.10

    Language：Japanese   Presentation type：Poster presentation  

    Venue：名古屋市  

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  • 抗CD40抗体とCOX-2阻害薬celecoxibの併用療法によるグリオーマに対する抗腫瘍免疫の誘導

    小坂朱, 大栗敬幸, 小林博也, 岡田秀穂

    第74回 日本癌学会学術総会 

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    Event date： 2015.10

    Language：English   Presentation type：Oral presentation (general)  

    Venue：名古屋市  

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  • マウス乳がんモデルを用いたSTINGアゴニストのがんの転移抑制に関する検討

    大栗敬幸, 石橋佳, 大原賢三, 平田結, 小坂朱, 長門利純, 青木直子, 及川賢輔, 原渕保明, 小林博也

    第74回 日本癌学会学術総会 

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    Event date： 2015.10

    Language：English   Presentation type：Poster presentation  

    Venue：名古屋市  

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  • A novel mechanism for activating Type-1 immunity by neuropeptide signaling through NK1R and NK2R in tumor microenvironments. International conference

    Takayuki Ohkuri, Junya Ohtake, Shun Kaneumi, Hidemitsu Kitamura, Hiroya Kobayashi

    The 10th International Symposium of the Institute Network “Towards the next generation research for cancer and immunology” 

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    Event date： 2015.7

    Language：English   Presentation type：Oral presentation (general)  

    Venue：Sapporo  

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  • マウス乳がん転移モデルを用いたSTINGライガンドとがんペプチドの併用療法の検討

    大栗敬幸, 石橋佳, 及川賢輔, 青木直子, 小林博也

    第104回 日本病理学会総会 

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    Event date： 2015.4 - 2015.5

    Language：Japanese   Presentation type：Poster presentation  

    Venue：名古屋市  

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  • EGFR阻害薬によって腫瘍から放出される抑制性サイトカインは抗腫瘍免疫を低下させうる

    熊井琢美, 大栗敬幸, 石橋佳, 及川賢輔, 青木直子, 小林博也

    第104回 日本病理学会総会 

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    Event date： 2015.4 - 2015.5

    Language：Japanese   Presentation type：Poster presentation  

    Venue：名古屋市  

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  • 抗腫瘍効果を有するアセチル化p53特異的T細胞の誘導とHDAC阻害剤によるアジュバント効果の検討

    石橋佳, 熊井琢美, 大栗敬幸, 及川賢輔, 青木直子, 木村昭治, 小林博也

    第104回 日本病理学会総会 

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    Event date： 2015.4 - 2015.5

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：名古屋市  

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  • Activation of antigen-specific T cells by neuropeptide signaling through neurokinin-2 receptor on human dendritic cells.

    Shun Kaneumi, Junya Ohtake, Mishie Tanino, Takuto Kishikawa, Satoshi Terada, Kentaro Sumida, Kazutaka Masuko, Toshiyuki Kita, Sadahiro Iwabuchi, Shinya Tanaka, Hiroya Kobayashi, Hidemitsu Kitamura

    第43回 日本免疫学会学術総会・学術集会 

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    Event date： 2014.12

    Language：English   Presentation type：Oral presentation (general)  

    Venue：京都市  

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  • 抗腫瘍効果を有するアセチル化p53特異的T細胞の誘導とヒストン脱アセチル化阻害剤によるアジュバント効果の検討

    石橋佳, 熊井琢美, 及川賢輔, 青木直子, 大栗敬幸, 木村昭治, 小林博也

    第94回北海道医学大会病理分科会・第47回北海道病理談話会 

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    Event date： 2014.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：旭川市  

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  • Activation of dendritic cells by neuropeptide signaling through NK1R and NK2R in neurogenic inflammation

    Shun Kaneumi, Junya Ohtake, Yosuke Ohno, Kentaro Sumida, Satoshi Terada, Takuto Kishikawa, Toshiyuki Kita, Hiroya Kobayashi, Hidemitsu Kitamura

    第73回 日本癌学会学術総会 

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    Event date： 2014.9

    Language：English   Presentation type：Poster presentation  

    Venue：横浜市  

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  • Induction of tumor-reactive T helper responses by a posttranslational modified epitope from tumor protein p53

    石橋佳, 熊井琢美, 及川賢輔, 小林博也

    第73回 日本癌学会学術総会 

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    Event date： 2014.9

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：横浜市  

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  • STING contributes to anti-glioma immunity via triggering type-I IFN signals in the tumor microenvironment

    Takayuki Ohkuri, Arundhati Ghosh, Akemi Kosaka, Saumendra N Sarkar, Hiroya Kobayashi, Hideho Okada

    第73回日本癌学会学術集会 

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    Event date： 2014.9

    Language：English   Presentation type：Oral presentation (general)  

    Venue：横浜市  

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  • STING contributes to anti-glioma immunity via triggering type-I IFN signals in the glioma microenvironment.

    大栗敬幸, 小林博也, 小坂朱, 岡田秀穂

    第110回北海道癌談話会例会 

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    Event date： 2014.9

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • 樹状細胞のNK1R・NK2Rを介した神経ペプチドシグナルによるType-1免疫の活性化機構

    北村秀光, 大竹淳矢, 金海俊, 大野陽介, 岸川拓斗, 寺田聖, 角田健太郎, 喜多俊行, 小林博也

    第18回 日本がん免疫学会総会 

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    Event date： 2014.7 - 2014.8

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：愛媛市  

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  • 樹状細胞のNK1R・NK2Rを介した神経ペプチドシグナルによるType-1免疫の活性化機 構

    北村秀光, 大竹淳矢, 金海俊, 大野陽介, 岸川拓斗, 寺田聖, 角田健太, 郎, 喜多俊行, 小林博也

    第18回 日本がん免疫学会総会 

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    Event date： 2014.7 - 2014.8

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：愛媛市  

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  • 左手掌の皮下腫瘤

    青木直子, 及川賢輔, 藤井 暁, 山本明美, 小林博也

    第30回日本皮膚病理組織学会学術大会 

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    Event date： 2014.7

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：東京都  

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  • 神経ペプチドシグナルはヒト樹状細胞のNK1RおよびNK2Rを介してType-1免疫を活性化する

    大竹淳矢, 金海俊, 谷野美智枝, 岸川拓斗, 寺田聖, 角田健太郎, 増子和尚, 喜多俊行, 岩淵禎弘, 田中伸哉, 小林博也, 北村秀光

    第79回 日本インターフェロン・サイトカイン学会学術集会 

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    Event date： 2014.6

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • 神経ペプチドシグナルはヒト樹状細胞のNK1RおよびNK2Rを介してType-1免疫を活性 化する

    大竹淳矢, 金海俊, 谷野美智枝, 岸川拓斗, 寺田聖, 角田健太郎, 増子和尚, 喜多俊行, 岩淵禎弘, 田中伸哉, 小林博也, 北村秀光

    第79回 日本インターフェロン・サイトカイン学会 

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    Event date： 2014.6

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • NK1R- and NK2R-dependent neuropeptide signaling regulates Type-1 immunity through activation of dendritic cells International conference

    Shun Kaneumi, Junya Ohtake, Kazutaka Masuko, Kentaro Sumida, Satoshi Terada, Takuto Kishikawa, Yosuke Ohno, Toshiyuki Kita, Hiroya Kobayashi, Hidemitsu Kitamura

    米国免疫学会総会 

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    Event date： 2014.5

    Language：English   Presentation type：Poster presentation  

    Venue：Pittsburgh  

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  • Activation of IL-6/STAT3-signaling cascade induces suppression of antigen presentation by human dendritic cells. International conference

    Hidemitsu Kitamura, Junya Ohtake, Shun Kaneumi, Kazutaka Masuko, Kentaro Sumida, Satoshi Terada, Takuto Kishikawa, Yosuke Ono, Toshiyuki Kita, Hiroya Kobayashi

    米国免疫学会総会 

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    Event date： 2014.5

    Language：English   Presentation type：Poster presentation  

    Venue：Pittsburgh  

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  • c- Met 及びオートファジーを標的としたヘルパー T 細胞による癌免疫治療の確立

    熊井琢美, 及川賢輔, 青木直子, 木村昭治, 小林博也

    第１０３回日本病理学会総会 

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    Event date： 2014.4

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：広島市  

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  • マウス急性肺障害における骨髄系細胞のMDL-1の機能と役割についての検討

    松田佳也, 青木直子, 熊井琢美, 及川賢輔, 木村昭治, 小林博也

    第１０３回日本病理学会総会 

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    Event date： 2014.4

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：広島市  

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  • Neuropeptide signaling activates Type-1 immunity through the NK1 and NK2 receptors on human dendritic cells International conference

    Hidemitsu Kitamura, Junya Ohtake, Shun Kaneumi, Kazutaka Masuko, Kentaro Sumida, Satoshi Terada, Takuto Kishikawa, Yosuke Ono, Toshiyuki Kita, Hiroya Kobayashi

    第１００回米国癌学会総会 

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    Event date： 2014.4

    Language：English   Presentation type：Poster presentation  

    Venue：San Diego  

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  • c-Met及びオートファジーを標的とした ヘルパーT細胞による癌免疫治療の確立

    熊井琢美, 小林博也, 原渕保明

    第32回 日本耳鼻咽喉科免疫アレルギー学会 

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    Event date： 2014.2

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：徳島市  

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  • 中年女性に発生した多発性肺病変

    及川賢輔, 松田佳也, 熊井琢美, 青木直子, 三代川斉之, 木村昭治, 小林博也

    第163回日本病理学会北海道支部学術集会 

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    Event date： 2014.1

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 中年女性にみられた孤立性肺腫瘍

    及川賢輔, 松田佳也, 熊井琢美, 青木直子, 佐藤啓介, 櫻井宏治, 木村昭治, 小林博也

    第163回日本病理学会北海道支部学術集会 

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    Event date： 2014.1

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • セツキシマブによる抗体依存性細胞傷害 活性はステロイドにより低下するのか？

    熊井琢美, 原渕保明, 小林博也

    第63回 北北海道耳鼻咽喉科懇話会 

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    Event date： 2014.1

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：旭川市  

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  • EGFR inhibition augments anti-tumor immune responses by HER family-specific human CD4 helper T cells in vitro. International conference

    Takumi Kumai, Yasuaki Harabuchi, Hiroya Kobayashi

    米国癌学会総会 

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    Event date： 2013.4

    Language：English   Presentation type：Poster presentation  

    Venue：Washington, DC  

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  • 腫瘍免疫におけるEGFR阻害薬のアジュバントとしての有用性

    熊井琢美, 小林博也, 原渕保明

    第３１回日本耳鼻咽喉科免疫アレルギー学会 

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    Event date： 2013.2

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • EGFR特異的CD4陽性ヘルパーT細胞クローンの誘導及びアジュバントについての検討

    熊井琢美, 原渕保明, 小林博也

    第28回 旭川集談会 

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    Event date： 2012.12

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：旭川市  

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  • アレルギーサイトカインであるIL-33の腫瘍における発現

    熊井琢美, 原渕保明, 小林博也

    第62回日本アレルギー学会秋季学術大会 

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    Event date： 2012.11 - 2012.12

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：大阪市  

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  • 食道粘膜下腫瘍の一例

    永田 真莉乃, 松田佳也, 熊井琢美, 青木直子, 佐藤啓介, 木村昭治, 櫻井宏治, 長谷川匡, 小林博也

    156回日本病理学会北海道支部学術集会 

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    Event date： 2012.11

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • 頭頚部癌に対するEGFR特異的ヘルパーT細胞免疫療法とEGFR阻害薬の相乗効果について

    熊井琢美, 松田佳也, 佐藤啓介, 青木直子, 木村昭治, 原渕保明, 小林博也

    第４５回北海道病理談話会 

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    Event date： 2012.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • HTLV-1+T細胞株MT２由来HLA-DR分子結合ペプチドは、成人T細胞白血病(ATL)細胞特異的Tヘルパーエピトープペプチドに成りうる

    小林博也, 熊井琢美, 松田佳也, 青木直子, 木村昭治, 佐藤啓介

    第４５回北海道病理談話会 

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    Event date： 2012.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • EGFR阻害薬によって増幅されるHER family特異的CD4ヘルパーT細胞の抗腫瘍効果について

    熊井琢美, 林 諭史, 松田佳也, 佐藤啓介, 原渕保明, 小林博也

    第７１回 日本癌学会学術総会 

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    Event date： 2012.9

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • EGFR由来ペプチドによるCD4陽性ヘルパーT細胞クローンの樹立

    熊井琢美, 小林博也, 原渕保明

    第1回 耳鼻咽喉科フロンティアカンファレンス 

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    Event date： 2012.9

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：旭川市  

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  • EGFR特異的CD4陽性ヘルパーT細胞クローンの誘導及びアジュバントについての検討

    熊井琢美, 松田佳也, 佐藤啓介, 青木直子, 木村昭治, 原渕保明, 小林博也

    第106回 北海道癌談話会例会 

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    Event date： 2012.9

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • 左上腕の皮膚結節

    青木直子, 佐藤啓介, 櫻井宏治, 山本明美, 小林博也

    第２８回日本皮膚病理組織学会 

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    Event date： 2012.7

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：東京  

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  • Tヘルパー応答から考察した肺癌の免疫標的抗原としてのEZH2,STEAPの有用性

    熊井琢美, 林諭史, 松田佳也, 佐藤啓介, 小林博也

    第１０１回日本病理学会総会 

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    Event date： 2012.4

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：東京  

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  • 特異な組織像を呈した子宮体癌の一例

    青木直子, 佐藤啓介, 小林博也

    第１５２回日本病理学会北海道支部学術集会 

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    Event date： 2012.3

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：札幌市  

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  • EGFR由来ペプチドによるCD４陽性ヘルパーT細胞クローンの樹立

    熊井琢美, 長門利純, 小林博也, 原渕保明

    日本耳鼻咽喉科免疫アレルギー学会 

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    Event date： 2012.2

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：滋賀  

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  • ヘルパーT細胞応答から考察した肺癌関連抗原としてのSTEAPおよびEZH2の有用性

    林 諭史, 立野正敏, 小林博也

    第70回日本癌学会学術総会 

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    Event date： 2011.10

    Language：Japanese   Presentation type：Poster presentation  

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  • 高齢者Ｓ状結腸穿孔の２例

    青木直子, 小林博也, 佐藤啓介

    第147回日本病理学会北海道支部学術集会 

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    Event date： 2011.5

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • シラカバ花粉症患者におけるＴ細胞受容体β鎖によるクローナリティ解析

    佐藤啓介, 青木直子, 小林博也, 木村昭治, 立野正敏

    第１００回日本病理学会総会 

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    Event date： 2011.4

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 高齢男性に発生したそけい部腫瘍

    青木直子, 小林博也, 佐藤啓介, 立野正敏

    第146回日本病理学会北海道支部学術集会 

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    Event date： 2011.3

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 膀胱頂部にみられた乳頭状病変

    立野正敏, 青木直子, 松田佳也, 林 諭史, 小林博也, 佐藤啓介, 岩崎沙理

    第145回日本病理学会北海道支部学術集会 

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    Event date： 2011.1

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 癌免疫、アレルギー制御に関わるHLAクラスII分子結合性ペプチド抗原の分子病理学的解析

    小林博也

    第56回日本病理学会秋期特別総会 

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    Event date： 2010.11

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

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  • ウイルス感染に伴う腎疾患の病理学的解析

    立野正敏, 林 諭史, 松田佳也, 青木直子, 佐藤啓介, 小林博也

    第43回北海道病理談話会 

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    Event date： 2010.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 癌に高発現するキナーゼを標的とした癌免疫療法の可能性

    小林博也, 林 諭史, 松田佳也, 青木直子, 佐藤啓介, 木村昭治, 立野正敏

    第43回北海道病理談話会 

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    Event date： 2010.10

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 若い女性二例にみられた子宮内膜病変

    立野正敏, 青木直子, 松田佳也, 林 諭史, 小林博也, 佐藤啓介, 柳内 充

    第143回日本病理学会北海道支部学術集会 

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    Event date： 2010.9

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 若い女性にみられた子宮頸部の腺肉腫

    立野正敏, 青木直子, 松田佳也, 林 諭史, 小林博也, 佐藤啓介, 柳内 充

    第141回日本病理学会北海道支部学術集会 

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    Event date： 2010.5

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • Ｔヘルパー応答から考察した癌抗原タンパク質としてのAurora-A kinaseの有用性

    小林博也, 林 諭史, 青木直子, 佐藤啓介, 木村昭治, 立野正敏

    第99回日本病理学会総会 

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    Event date： 2010.4

    Language：Japanese   Presentation type：Oral presentation (general)  

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  • 泡沫状胞体を示す巨細胞癌の形態をとった甲状腺未分化癌の一例

    立野正敏, 青木直子, 小林博也, 佐藤啓介, 柳内 充, 高田明生

    第99回日本病理学会総会 

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    Event date： 2010.4

    Language：Japanese   Presentation type：Poster presentation  

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  • 汎血球減少を示したIgG4関連リンパ節炎の一例

    立野正敏, 木村昭治, 林 諭史, 安住 誠, 青木直子, 小林博也, 佐藤啓介, 及川賢介, 桜井宏治

    第140回日本病理学会北海道支部学術集会 

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    Event date： 2010.3

    Language：Japanese   Presentation type：Oral presentation (general)  

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Industrial property rights

  • SARS-CoV-2由来のT細胞エピトープペプチド

    大栗敬幸, 小林博也, 矢島優己, 他施設共同研究者

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    Application no：PCT/JP2022/021153  Date applied：2022.5

    Country of applicant：International (PCT) application  

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  • SARS-CoV-2由来のT細胞エピトープペプチド

    大栗敬幸, 矢島優己, 小林博也

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    Application no：2021-86285  Date applied：2021.5

    Country of applicant：Domestic  

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  • がん抗原ペプチド

    大栗敬幸, 小坂 朱, 小林博也

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    Application no：6857930  Date applied：2021.3

    Country of applicant：Domestic  

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  • がん抗原ペプチド

    大栗敬幸, 小坂 朱, 小林博也

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    Application no：PCT/JP2019/005623  Date applied：2019.2

    Country of applicant：International (PCT) application  

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  • がん抗原ペプチド

    大栗敬幸, 小坂朱, 小林博也

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    Application no：特願2018-024972  Date applied：2018.2

    Country of applicant：Domestic  

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  • がん抗原ペプチド

    大栗敬幸, 小坂朱, 小林博也

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    Application no：2017-072183  Date applied：2017.3

    Country of applicant：International (PCT) application  

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  • がん免疫療法に利用可能な抗原性ポリペプチド及び当該ポリペプチドを含む抗腫瘍剤

    大栗敬幸, 石橋桂, 熊井琢美, 小林博也

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    Application no：2016-041834  Date applied：2016.3

    Country of applicant：International (PCT) application  

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Awards

  • 日本病理学会学術研究賞（A演説）

    2010.11   日本病理学会  

    小林博也

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    Award type：Award from Japanese society, conference, symposium, etc.  Country：Japan

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Research Projects

  • 頭頸部癌特異的T細胞を活用した複合型免疫療法の開発

    Grant number：23K08977  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    熊井 琢美, 小林 博也

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    Grant amount：\4,680,000 （ Direct Cost: \3,600,000 、 Indirect Cost：\1,080,000 ）

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  • cGAS/STING/I型IFN経路を基軸とした癌免疫微小環境のホット化治療戦略 研究課題

    Grant number：22H02838  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    小林 博也, 小坂 朱, 大栗 敬幸, 長門 利純

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    Grant amount：\17,420,000 （ Direct Cost: \13,400,000 、 Indirect Cost：\4,020,000 ）

    cGAS/STING/I型IFN経路を基軸とした癌免疫微小環境のホット化治療戦略

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  • Epithelial mesenchymal transition (EMT)-associated proteins as potent immunotherapeutic target for canner immunotherapy

    Grant number：19K07452  2019.4 - 2022.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Kobayashi Hiroya

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    Grant amount：\4,290,000 （ Direct Cost: \3,300,000 、 Indirect Cost：\990,000 ）

    During metastasis, cancer cells often obtain unique characteristics such as epithelial-mesenchymal transition (EMT). Vimentin is one of the biomarkers that contributes to EMT by changing cell shape and motility. Since abnormal phosphorylation is a hallmark of malignancy, targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors.Here, we showed that the expression of phosphorylated vimentin was upregulated in metastatic sites of Colorectal cancer (CRC). The novel phosphorylated helper peptide epitopes from vimentin could elicit sufficient T cell response. Notably, precursor lymphocytes which specifically reacted to these phosphorylated vimentin-derived peptides were detected in CRC patients.
    These results suggested that immunotherapy targeting phosphorylated vimentin could be a novel therapeutic agent for metastatic CRC patients.

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  • Analysis of stealth antigens for developing tumor immunotherapy

    Grant number：16K15244  2016.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Kobayashi Hiroya

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    Grant amount：\3,640,000 （ Direct Cost: \2,800,000 、 Indirect Cost：\840,000 ）

    We found several stealth antigens which are epigenetically suppressed in tumor cells due to their high antigenicity and re-transcripted and -translated by treating with DNA methyltransferase inhibitor. We found that the stealth antigen-specific Th cells were efficiently generated from peripheral blood mononuclear cells from healthy donors. Also combination therapy of the Th cells and DNA methyltransferase inhibitor efficiently inhibited growth of human cancer cell line in immunodeficient mice.

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  • Development of novel diagnosis and therapeutic procedures for nasal NK/T-cell lymphoma consists of targeting EBV-associated molecules

    Grant number：15H04986  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Harabuchi Yasuaki

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    Grant amount：\16,640,000 （ Direct Cost: \12,800,000 、 Indirect Cost：\3,840,000 ）

    We generated murine xenograft models inoculated with an natural killer/T-cell lymphoma cell line and revealed that sPD-L1 could be a prognostic predictor for NNKTL and open up the pos- sibility of immunotherapy of this lymphoma using PD-1/ PD-L1 axis inhibitors.
    We revealed that circulating EBV‐miRNAs, particularly miR‐BART2‐5p, may serve as potential diagnostic and prognostic biomarkers in patients with nasal natural killer/T-cell lymphoma.

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  • Assessment of T-cell based immunotherapy targeting EGFR with immune-molecular targeted combination therapy for treatment of reflactory cancer.

    Grant number：25460430  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KOBAYASHI Hiroya

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    Grant amount：\5,200,000 （ Direct Cost: \4,000,000 、 Indirect Cost：\1,200,000 ）

    We evaluated the capacity of predicted CD4 T-cell peptide epitopes from HER family to induce anti-tumor immune responses. Among several predicted peptide epitopes, EGFR875-889 elicited CD4 T cell responses that were restricted by several HLA-DR alleles, indicating that the peptide functions as a promiscuous T cell epitope. The CD4 T cells were capable of directly recognized and killed HNSCC or lymphoma cells expressing antigens. Finally, we examined whether an EGFR tyrosine kinase inhibitor would affect CD4 T cell tumor reactivity. Treatment of tumor cells with the EGFR inhibitors enhanced tumor recognition by EGFR875-889 reactive T cells presumably due to the up-regulation of HLA-DR expression in the tumor cells. The results demonstrate the utility of EGFR inhibitors as immune modulators. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of maligancies and rational explanation for immune-targeted combination therapy.

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  • 癌ワクチン治療開発に向けたヒト免疫応答・癌組織解析等に関する研究

    2012.4 - 2016.3

    北海道大学 

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  • A foundational study for targeted therapy against EB virus and tumor growth factor in nasal NK/T-cell lymphoma

    Grant number：24390385  2012.4 - 2015.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    HARABUCHI Yasuaki, TAKAHARA Miki, KISHIBE Kan, KOBAYASHI Hiroya, UEDA Seigo, NAGATO Toshihiro, KOMABAYASHI Yuki

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    Grant amount：\18,330,000 （ Direct Cost: \14,100,000 、 Indirect Cost：\4,230,000 ）

    Nasal natural killer/T cell lymphoma (NNKTL) is Epstein-Barr virus (EBV)-associated malignancy and characterized by a poor prognosis. In the present study, we found that CD70 was specifically expressed in NNKL cell lines and that it played a role in cell growth by binding to soluble CD27. Moreover, we found that CCL17 and CCL22 was upregulated in NNKTL cell lines and CCR4 was observed on NNKTL cell lines. In addition, we showed that anti-CD70 and anti-CCR4 antibodies could induce complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against NKKTL cells, respectively. Furthermore, we revealed that microRNA (miR)-15a was downregulated in NNKTL cell lines and that miR-15a led to decreased expression of MYB and cyclin D1, thereby resulting in inhibition of cell proliferation.

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  • Developing T-cell based immunotherapy using ubiquitously expressing tumor-associated antigen, Aurora-A kinase and FAK

    Grant number：21590424  2009.4 - 2012.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    KOBAYASHI Hiroya

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    Grant amount：\4,680,000 （ Direct Cost: \3,600,000 、 Indirect Cost：\1,080,000 ）

    Focal adhesion kinase (FAK) and Aurora kinase A (Aurora-A) are ubiquitously expressed kinase involved in cancer progression and with poor prognosis that are found overexpressed in various types of cancer. To validate FAK and Aurora-A as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and cancer patients. Synthetic peptides correspond to potential HTL epitopes induced HTL responses that directly recognized FAK/Aurora-A-expressing tumor cells and autologous dendritic cells pulsed with these TAA-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK/Aurora-A peptides were recognized by cancer patient's CD4 T cells, the T helper peptide epitopes might be used for designing T cell-based immunotherapy for FAK/Aurora-A-expressing cancers.

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  • Fundamental investigation aimed at EB virus-targeted therapy for nasal NK/T-cell lymphoma.

    Grant number：20390438  2008.4 - 2011.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    HARABUCHI Yasuaki, TAKAHARA Miki, KISHIBE Kan, KOBAYASHI Hiroya, KATAYAMA Akihiro, NAGATO Toshihiro

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    Grant amount：\14,560,000 （ Direct Cost: \11,200,000 、 Indirect Cost：\3,360,000 ）

    Nasal NK/T cell lymphoma is Epstein-Barr virus(EBV)-related and poor prognosis malignancy. In this study, we found that chemokine IP-10 (Interferon gamma-induced protein-10) was produced by EBV positive Nasal NK/T cell lymphoma cell lines, and the IP-10 enhanced invasive potential of the cells in autocrine manner. Moreover, we revealed that monocytes attracted by IP-10 enhanced proliferation and LMP-1 expression of the cells by cell-contact manner via membrane-bound IL-15. Currently, we are studying about CD70 and LFA-1, which can be regulated by EBV. On clinical studies, we are trying arterial infusion chemotherapy from superficial temporal artery in combination with radiotherapy for early stage nasal NK/T-cell lymphoma. Effect of the treatments was evaluated by serum EBV-DNA copy number, as well as local findings, CT, and MRI. All of 9 patients treated by this approach were in complete remission, and no sign of relapse has seen in the patients.

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  • HLA分子による免疫制御機構の研究

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    Grant type：Competitive

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  • HLA分子結合腫瘍関連抗原ペプチドによる効果的な抗腫瘍ヘルパーT細胞の樹立とその活性化の機構の解明

    科学研究費補助金 

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  • Study on mechauism of immunoregulation by HLA moleles

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    Grant type：Competitive

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Academic Activities