| Project/Area Number |
22KF0193
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| Project/Area Number (Other) |
22F21409 (2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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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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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2023: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2022: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | scRNA-Seq / Cancer immunotherapy / EGFR / lung cancer / NK / NSCLC |
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| Outline of Research at the Start |
1.Validate the presence of uNK correlated with CD8T cells activation in NSCLC
2.Examine the presence of uNK in normal lung tissue and compare the signature of uNK in lung normal and tumor tissues
3.Study which mouse cell line can form a tumor with uNK infiltration for further functional studies
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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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