2023 Fiscal Year Final Research Report
Uncovering the biology of new immune-checkpoint molecule inhibitor and that impact for micro immune microenvironment
| Project/Area Number |
22K16794
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | 腎細胞癌 / 癌免疫微小環境 / TIGIT / 免疫チェックポイント阻害剤 |
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| Outline of Final Research Achievements |
Cancer immuno therapy brought the great benefit to medical oncology, however some metastatic renal cell carcinoma (mRCC) patients showed primary resistance. In recent years, anti-LAG-3 antibody has been launched as a new treatment. We evaluated the clinical impact and the immune-microenvironment related with the other novel immune-chckpoint molecule, TIGIT in mRCC patients. The result showed high TIGIT expression mRCC patients showed good prognosis. High TIGIT expression was related with higher CD8+, FOXP3+, that showed exhausted T cell envrironment, with higher PD-1+, PD-L1+, that showed TIGIT is corelated with other immunecheckpoint molecules, and with higher CD68, CD163, that showed tumor associated immune-repressive environment. This clinical impact and TIGIT related immune-microenvironment characterics was varidated in the other clinical trial cohort.
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| Free Research Field |
癌免疫微小環境
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| Academic Significance and Societal Importance of the Research Achievements |
TIGITは次世代癌免疫療法の標的分子として注目されるが、その免疫微小環境は不明である。今回我々はTIGIT発現の臨床的有用性に始まり、微小環境の特徴を評価し、かつそれを複数の大規模コホートで確認した。この結果はこれまでに腎細胞癌では報告されておらず、ここに学術的意義がある。
また、新規癌免疫療法は一定の効果を認める一方で、効果を認めない症例が一定数存在することが特徴である。治療有効または治療不応が予測される症例を選出するためにはその生物学的評価が重要となる。本研究成果は高額な新規癌免疫療法を適切な患者に届けることで、医療経済へのメリットにも繋がることが期待される。
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