Organization
Hospital Central Clinical Facilities Oncology Center
External link
SARASHINA Takeo
Degree
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Doctor of Medicine ( 2014.3 Asahikawa Medical College )
Research Projects
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Search into the mechanism of B7-H3 expressing MDSC generation by liposome and its T cell suppression
Grant number：19K08854 2019.4 - 2022.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Azuma Hiroshi
Grant amount：\4,420,000 （ Direct Cost: \3,400,000 、 Indirect Cost：\1,020,000 ）
We found that injection of liposome into rat transiently induce accumulation of cells in spleen that have the potential to suppress T cell proliferation. These cells are splenic macrophages which internalized liposome and expressed B7-H3 molecule on their surface. Execution of the suppressive function require cell-to-cell contact and the direct effector for suppression is nitric oxide. They are positive for iNOS. NFkB and all MAP kinase (ERK1/2, JUK, and p38) were shown to be activated. Based on these findings, we concluded that these cells are similar to B7-H3 positive myeloid derived suppressor cells(MDSC) which infiltrated in the tumor. In addition, we found that the main pathway for the endocytosis of liposome used in the experiment is macropinocytosis.
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Mechanism of B7-H3 expression on liposome induced MDSC-like cell and its influence on immunosuppression
Grant number：16K10010 2016.4 - 2020.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Hiroshi Azuma
Grant amount：\4,810,000 （ Direct Cost: \3,700,000 、 Indirect Cost：\1,110,000 ）
We had reported that when some liposome was injected into rat, immunosuppressive macrophages were induced in rat spleen and these macrophages meets some of the criteria for myeloid derived suppressor cells. In this study, we revealed that these macrophages are positive for B7-H3 molecule on their surface and they have the ability to suppress T cell proliferation. In addition, we reveled that splenocyte derived form liposome-loaded rat express iNOS and NFkB signaling pathways in these cells are activated. However, anti-B7-H3 antibody failed to restore T cell proliferation.