| Project/Area Number |
21F20405
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-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) |
ZOU YIXIN 京都大学, 医学研究科, 外国人特別研究員
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| Project Period (FY) |
2021-04-28 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2022: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2021: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | BTK inhibitor / Xbp1s / CD8+ T cells / PD-1 blockade therapy / combination therapy |
|---|
| Outline of Research at the Start |
1. Choosing and constructing suitable cell lines.
2. Constructing tumor-bearing mice and comparing the efficacy of single therapy and combination therapy.
3. Exploring the number and functions of total and tumor-reactive CD8+ T cells in draining lymph nodes and tumor sites during therapy.
|
| Outline of Annual Research Achievements |
Acalabrutinib could change the metabolic patterns of CD8+ T cells in vivo, but failed in vitro. Both BTK inhibitors could reduce UPR genes expression in CD8+ T cells, especially for Xbp1s. The expression of Xbp1s was up-regulated in tumor-infiltrating CD8+ T cells compared with those from DLNs and tumor-free LNs. In addition, the Xbp1s expression showed negative correlation with Ifng, Gzmb and Prf1 in tumor-infiltrating CD8+ T cells. Similarly, in vitro experiments revealed that Xbp1s overexpressed CD8+ T cells had lower levels of interferon-gamma, granzyme B and perforin than wild type. By analyzing the GEO dataset GSE118430, we found that Xbp1 KO CD4+ T cells showed relatively high expression of several genes associated with T cells immune response such as Ifng, Ccl5, Cxcr5, etc.
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| Research Progress Status |
令和4年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和4年度が最終年度であるため、記入しない。
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