2023 Fiscal Year Annual Research Report
EBV抗原発現調節による、EBV関連胃癌に対する効果的ながん免疫療法の開発
| Project/Area Number |
22KF0193
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| Allocation Type | Multi-year Fund |
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| Research Institution | Kyoto University |
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Principal Investigator |
本庶 佑 京都大学, 医学研究科, 特任教授 (80090504)
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| Co-Investigator(Kenkyū-buntansha) |
LEONG MAN LONG 京都大学, 医学研究科, 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Keywords | scRNA-Seq / Cancer immunotherapy / EGFR / lung cancer |
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| Outline of Annual Research Achievements |
Good response to ICI therapies in EBVaGC has been proposed due to the EBV antigens presentation and high expression of PD-L1. Since EBV infection in lung cancer (LC) is uncommon, other factors may contribute to the ICI therapy response in LC. As LC paitents with PD-L1 high, the only clinically approved marker for ICI therpay in LC, are not always response to ICI therapy, the aim of this project is to identify effective markers to ICI therapy in LC.In discovery phase, by using scRNA-Seq comparing LC patients of 4 responders (RP) and 4 non-responders (NRP), we found a group of cells (Y) from the peripheral blood (PB) of the NRP highly expressed a gene (X). This result was further validated by FACS from validation cohort composed 87 LC patients.From surgical cohort composed of 12 LC paitents’ PBMC and tumors, we could also identify X-expressing Y cells from all those tissues, suggesting the expression of X in Y cells have a role in the TME of NRP. From tumors of the surgical cohort, we also found a lower proportion of another cluster of cells (Z) from the EGFR-Mut compared with EGFR-WT. Given that EGFR-Mut is usually resistant to ICI therapy, we supposed Z cells has a supportive role to T-cell activation.We further found the signature genes of Z cells is positively correlated with T-cell activation in the tumor. Overall, our results showed Z cells potentiate T-cell activation in TME. We also identified and validated X high in Y cells from PB is associated with NRP to ICI therapy in LC. This finding is currently under patent application as a biomarker for ICI therapy in LC.
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