| Project/Area Number |
16K08663
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平岡 伸介 国立研究開発法人国立がん研究センター, 中央病院, 科長 (40276217)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 免疫微小環境 / 膵がん / 血管内皮細胞 / がん微小環境 / 内皮細胞 / がんの免疫微小環境 / 病理学 |
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| Outline of Final Research Achievements |
Cancer microenvironment is very important for characterizing the behaviors of cancer. Here we investigated roles of the endothelial cells in pancreatic cancer (PDAC) immune microenvironment. We analyzed gene expression profiles of endothelial cells isolated from fresh PDAC tissues or chronic pancreatitis tissues. Gene X expressed significantly higher in PDAC tissues than in non-cancerous tissues and molecule X expressed in a part of endothelial cells in PDAC tissues but not in non-cancerous tissues. Patients of PDAC with higher density of molecule X-expressing endothelial cells had a significantly longer survival both for overall survival and disease-free survival. It is suggested that molecule X-expressing endothelial cells are involved in the activation of CD4+ T cells. This is the first study to show endothelial cells in cancer tissues contribute to activation of CD4+ T cells.
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| Academic Significance and Societal Importance of the Research Achievements |
がん微小環境はがんの生物学的特性の決定に寄与し、その形成機序の解明はがんの生物学の解明とがん治療の標的探索に重要である。本研究ではがん免疫微小環境における血管内皮細胞の役割について検討し、これまで知られていなかった、がん組織内血管内皮細胞がCD4+T細胞を活性化する新たな事象を新しく発見した。膵がんは極めて難治性で、免疫チェックポイント阻害剤による最近の免疫治療にも抵抗性である。本研究により発見された分子X発現血管内皮細胞を利用し、既存の免疫療法と組み合わせることで治療効果の向上が期待される。難治性膵がんの治療選択肢が広がるようになれば、国民の保険・医療に寄与するところが大きい。
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