| Project/Area Number |
25430148
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
KAKIMI Kazuhiro 東京大学, 医学部附属病院, 特任教授 (80273358)
KUME Haruki 東京大学, 医学部附属病院, 登録研究員 (10272577)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 腎がん / 次世代シーケンス / 遺伝子変異 / MHCクラスI結合予測法 / 免疫チェックポイント分子 / ネオアンチゲン / 個別化がん免疫治療 / 固有抗原 / ミスセンス変異 / 変異ペプチド / MHC class I 結合予測法 / アフィニティ / 免疫反応 / 全RNA シーケンス / 全エクソームシーケンス |
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| Outline of Final Research Achievements |
We established a method to identify neoantigens derived from tumor-specific mutations by combining next generation sequencing (NGS) with MHC class I binding algorism. In 97 clear cell renal cell carcinoma (ccRCC), we demonstrated that patients with high neoantigen load and HLA expression correlated with better clinical outcomes and also they expressed high CD8A, perforin and granzyme A. However, immunosuppressive molecules such as CTLA-4 and PD-1 were also highly expressed in the tumor, suggesting that abundant neoepitopes associated with greater antitumor effector immune responses were counterbalanced by a strongly immunosuppressive microenvironment. We have created the system predicting candidate neoantigens and showed that neoantigen load, antigen presentation machinery, and immune signatures determine prognosis in ccRCC. They are prerequisites for individualized cancer immunotherapy development in the patients.
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