| Project/Area Number |
18K15219
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Kagoshima University |
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Principal Investigator |
Tanoue Kiyonori 鹿児島大学, 鹿児島大学病院, 特任助教 (50721031)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 膵臓癌 / 免疫チェックポイント分子 |
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| Outline of Final Research Achievements |
Pancreatic cancer is called “cold tumor” because the number of cytotoxic T cell (CTL) in tumor-infiltrating lymphocytes is extremely small. However, some cases of pancreatic cancer in this study had “hot tumor” in which a large number of CTLs were observed, and overall survival was significantly longer in patients with a large number of CTL. In these pancreatic cancer tissues, expression of PD-L1 and PD-L2 were not observed. Meanwhile, expression of immune checkpoint ligand such as Galectin-9, a ligand of Tim-3, was observed. Moreover, overall survival was significantly longer in the cases with low expression of Galectin-9, so it is considered that Galectin-9 may be an immunosuppressive factor in pancreatic cancer. These results suggest that the Tim-3/Galectin-9 pathway may be a useful target pathway for immune checkpoint inhibition therapy for pancreatic cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤の治療効果が認められ、消化器癌でも免疫療法が実臨床で用いられるようになってきた。しかし、膵癌においては臨床試験でも他の癌種に比べ十分な効果が得られず、適用が進んでいない。理由として膵癌の微小環境において免疫が著しく不活化されていることが挙げられ、そのため免疫療法の確立が困難であると考えられている。本研究は、膵癌切除標本を用いて免疫環境の解析を行い、免疫療法の効果を改善させるための標的分子を同定することを目的とした。今後さらに遺伝子変異も含めた膵癌の免疫抑制メカニズムを解析することにより、新規の膵癌免疫療法の開発に繋げ、膵癌患者の予後の改善を目指す。
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