| Project/Area Number |
18K15226
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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 | Kawasaki Medical School |
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Principal Investigator |
KUROSE KOJI 川崎医科大学, 医学部, 講師 (30551139)
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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 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 癌性胸水 / 免疫チェックポイント分子 / Treg / がん性胸水 / がん免疫微小環境 / 化学療法 |
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| Outline of Final Research Achievements |
To analyze the immune microenvironment in lung cancer, tumor infiltrating immunocompetent cells and tumor cells in malignant pleural effusion were analyzed by flow cytometry. From January 2011 to March 2017, a retrospective analysis was performed on 45 malignant pleural effusion cases for which research consent was obtained at our hospital. In malignant pleural effusion, many memory CD4 T cells and CTLA-4 positive Treg cells were accumulated, PD-L1 expression in tumor cells and macrophages was high, and T cells proliferation was suppressed. It is considered that these strong immunosuppressive environments affect the poor efficacy and poor prognosis of immunotherapy, and the development of treatments to restore the immunosuppressive environment is needed.
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| Academic Significance and Societal Importance of the Research Achievements |
癌性胸水中にはPD-L1陽性腫瘍細胞やマクロファージが多く存在し、さらにはCTLA-4陽性Tregが浸潤することにより強い免疫抑制環境を形成しており、結果としてT細胞機能が抑制されていることが示唆された。このような免疫抑制状態にある癌性胸水環境に対し、今後免疫チェックポイント分子阻害薬の胸腔内への局所投与や、Tregや抑制性マクロファージに対する治療としての化学療法併用治療が有用となる可能性が期待される。
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