Regulation of oxidative metabolic product-mediated immune suppressive tumor microenvironment to improve the efficacy of immune checkpoint blockade therapy in cancers.

Research Project

Project/Area Number	19K16808
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 50020:Tumor diagnostics and therapeutics-related
Research Institution	Keio University
Principal Investigator	Sayem Mohammad Abu 慶應義塾大学, 医学部(信濃町), 特任助教 (80772920)
Project Period (FY)	2019-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords	VAP-1 inhibitor / Immunosuppression / H2O2 / CTLs / ICIs / ICBs
Outline of Research at the Start	The mechanisms of tumor inhibition of MC-38 mouse model by VAP-1 inhibition with specific inhibitor will be identified. We expect that the reduction of ROS due to inhibition of VAP-1 enzymatic function would be the cause to relieve the immunosuppression and will also synergize with the ICBs.
Outline of Final Research Achievements	Immunotherapy is a promising treatment modality for cancer. In this study we showed that inhibition of vascular adhesion protein 1, partly responsible for generating immunosuppressive microenvironment, can reverse the unfavorable immune-environment and synergize with current approve immunotherapy.
Academic Significance and Societal Importance of the Research Achievements	This study showed that oxidative tumor microenvironment can generate immunosuppressive element. This immunosuppression can be altered by inhibiting a particular adhesion protein. This information may help to revise patient care for immunotherapy.