2020 Fiscal Year Annual Research Report
Regulation of oxidative metabolic product-mediated immune suppressive tumor microenvironment to improve the efficacy of immune checkpoint blockade therapy in cancers.
| Project/Area Number |
19K16808
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | VAP-1 inhibitor / H2O2 / Immunosuppression / CTLs / ICBs |
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| Outline of Annual Research Achievements |
In this study, the role of VAP-1 in TME was investigated. Intraperitoneal administration of the VAP-1-specific inhibitor U-V296 inhibited murine tumor growth by enhancing IFN-γ-producing tumor antigen-specific CD8+ T cells. U-V296 exhibited significant synergistic anti-tumor effects with ICIs. In the TME of mice treated with U-V296, the expressions of genes associated with immunosuppression were significantly decreased. H2O2, which promoted the production of IL-4 by mouse Th2 and inhibited IFN-γ by mouse Th1 and human tumor-infiltrating lymphocytes, was decreased. These results indicated that VAP-1 is involved in the immunosuppressive TMEs through H2O2-associated Th2/M2 conditions and may be an attractive target for the development of combination cancer immunotherapy with ICIs.
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