Organization
School of Medicine Medical Course Basic Medicine Pathology[Immuno Pathology]
External link
KOSAKA Akemi
Research Areas
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Life Science / Immunology
Research Projects
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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
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
Grant amount：\17,420,000 （ Direct Cost: \13,400,000 、 Indirect Cost：\4,020,000 ）
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STINGアゴニストを用いたTNBCに対する効果的ながん免疫療法の開発
Grant number：22K06955 2022.4 - 2025.3
日本学術振興会 科学研究費助成事業 基盤研究(C)
小坂 朱
Grant amount：\4,160,000 （ Direct Cost: \3,200,000 、 Indirect Cost：\960,000 ）
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Induction of type I IFN in the immunosuppressive tumor microenvironment
Grant number：18K07009 2018.4 - 2021.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Kosaka Akemi
Grant amount：\4,550,000 （ Direct Cost: \3,500,000 、 Indirect Cost：\1,050,000 ）
We performed real-time PCR and RNA sequencing analysis of tumor-associated macrophages derived from mouse tumor tissues. It was found that STING agonist induced higher levels of type I IFN compared with TLR agonists and TLR3 agonist induced lower levels of genes associated with DNA sensors and TLR-signaling pathways. In using mouse born-marrow derived immunosuppressive macrophages, agonists of not only TLR3 but also TLR4, TLR7 and TLR9 showed decreased type I IFN expression. Furthermore, it was suggested that IL-13 signaling may contribute to decreased induction of type I IFN expression by TLR agonists in the immunosuppressive microenvironment.
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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
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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Cancer immunotherapy by combining the selective COX-2 inhibitor and type I IFN signaling
Grant number：16K19071 2016.4 - 2018.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
KOSAKA Akemi
Grant amount：\3,900,000 （ Direct Cost: \3,000,000 、 Indirect Cost：\900,000 ）
The aim for this study is to development of an efficient and convenient cancer immunotherapy and to elucidate the mechanism when combining the selective COX-2 inhibitor celecoxib and the type I IFN inducer 2’3’-cGAMP.We used different mouse tumor models to determine the treatment regimen of celecoxib and 2’3’-cGAMP. The combination therapy showed a significant antitumor effect on tumor growth in mice compared to control and monotherapy with celecoxib or 2’3’-cGAMP. The antitumor effect of the combination therapy was not dependent on CD8+ T-cells and macrophages, and it was suggested that the type I IFN signaling pathway may not be involved in the antitumor responses of the combination therapy.