| Project/Area Number |
17K16853
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 抗腫瘍免疫 / CD8 T細胞 / 細胞内エネルギー代謝 / 腫瘍免疫 / 婦人科腫瘍 / 免疫療法 / 免疫調節 |
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| Outline of Final Research Achievements |
The antitumor activity of activated CD8 T cells in the tumor microenvironment seems to be limited due to their being metabolically unfit. We therefore assessed the role of glutamine metabolism in the antitumor activity of CD8 T cells using a tumor-inoculated mouse model. The adoptive transfer of tumor-specific CD8 T cells cultured under glutamine-restricted (dGln) conditions or CD8 T cells treated with specific inhibitors of glutamine metabolism efficiently eliminated tumors and led to a better survival of tumor-inoculated mice than with cells cultured under control (Ctrl) conditions. The decreased expression of PD-1 and increased Ki67 positivity among tumor-infiltrating CD8 T cells cultured under dGln conditions suggested that the inhibition of glutamine metabolism prevents CD8 T-cell exhaustion in vivo. Given these findings, our study uncovered an important role of glutamine metabolism in the antitumor activity of CD8 T cells.
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| Academic Significance and Societal Importance of the Research Achievements |
グルタミン代謝を抑制したCD8 T細胞の培養を行ったところ、細胞の疲弊が抑制され、通常培養に比べて抗腫瘍活性が増強されることが明らかとなった。そのメカニズムとして、我々は、低グルタミン培養によりCD8 T細胞のメモリー分化が促進することを明らかにした。腫瘍特異的なCD8 T細胞内のグルタミン代謝の抑制は、メモリー分化を促進し、腫瘍微小環境下でも疲弊を免れ増殖を続け、結果として効果的な腫瘍細胞の除去につながると考えられ、腫瘍特異的CD8 T細胞の養子免疫療法として将来、有効な培養方法になることが期待される。
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