Analysis of rRNA methylation in tumor immune system though PD-1
| Project/Area Number |
17K07164
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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 biology
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| Research Institution | Kyoto University |
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Principal Investigator |
Waku Yuka 京都大学, 医学研究科, 研究員 (40399499)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | rRNA / 塩基メチル化 / 腫瘍免疫 / PD-1 |
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| Outline of Final Research Achievements |
In this study, I performed FACS analysis using specific antibodies and found that the positive cells of N1-methyladenosime (m1A) was increased in highly differentiated CD8+ T-cell subsets which expressed m1A methyltransferase NML. Moreover, the percentage of m1A positive CD8+ T-cells in young mice was increased by PD-1 blockade therapy. On the other hand, the induction in aged mice, that could not reject tumors, was not induced by PD-1 blockade. These results suggest that m1A RNA modification is involved in the activation of CD8+ T-cells through PD-1 blockade.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでにタンパク質合成制御を調節するための修飾として考えられてきたrRNAのメチル化が、腫瘍免疫機能を制御するという全く新しい機能の解明を推し進め普遍性を追求する本研究は、RNA修飾分野のみならず免疫の分野において、パラダイムシフトを引き起こすものと考える。また、本研究により得られたPD-1経路阻害に対する不応答性がんの問題の克服に繋がる成果は、新しいがん免疫療法の開発に繋がるのみならず、PD-1阻害治療の有効性を判断するためのバイオマーカー開発にも繋がると予想される。治療前に不応答患者かどうかを判定出来れば、抗体治療という高額医療費の削減にも繋がり得ると考えられる。
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Report
(4 results)
Research Products
(5 results)
