Exploration of molecular targets to regulate cancer-associated fibroblasts-mediated immunosuppression in the tumor microenvironment
Project/Area Number |
17K11374
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Otorhinolaryngology
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Research Institution | Gunma University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 頭頸部癌 / 癌関連線維芽細胞 / 癌 |
Outline of Final Research Achievements |
Tumor cells create immunosuppressive network with various stromal cells in the tumor microenvironment. Among various types of stromal cells, cancer-associated fibroblasts (CAFs) have been recognized as one of key component for escape from host antitumor immunity. In this study, we detected AKT3 as a common molecule mediated immune suppression in both cancer cells and CAFs. AKT3 expression in tumor cells and CAFs was a prognostic factor in oral squamous cell carcinoma, respectively. Moreover, knockdown of AKT3 expression in tumor cells and CAFs resulted in significant inhibition of cellular proliferation, cytokine production, and expression of immune regulatory molecules.
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Academic Significance and Societal Importance of the Research Achievements |
がん局所は免疫抑制状態となっており、このことが治療抵抗性や予後不良と関係している。今回の研究において、癌細胞と癌関連線維芽細胞(CAFs)の免疫抑制機能を制御できる共通の分子(AKT3)が同定できたことにより、この分子を標的とした新規薬剤の開発につながる可能性がある。このような薬剤は効率的にがん局所の免疫抑制状態を改善させ、現在限定的な効果を示す免疫チェックポイント阻害剤との併用により、その治療効果の改善に寄与できるかもしれない。また、AKT3は予後予測因子としてのバイオマーカーとして利用できる可能性がある。
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Report
(4 results)
Research Products
(25 results)
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[Journal Article] Carbon-ion radiotherapy combined with chemotherapy for head and neck mucosal melanoma: Prospective observational study.2019
Author(s)
Takayasu Y, Kubo N, Shino M, Nikkuni O, Ida S, Musha A, Takahashi K, Hirato J, Shirai K, Saitoh JI, Yokoo S, Chikamatsu K, Ohno T, Nakano T; Working Group on Head and Neck Tumors.
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Journal Title
Cancer Med.
Volume: 8
Issue: 17
Pages: 7227-7235
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck.2017
Author(s)
Shirai K, Saitoh J, Musha A, Abe T, Kobayashi D, Takahashi T, Tamaki T, Kawamura H, Takayasu Y, Shino M, Toyoda M, Takahashi K, Hirato J, Yokoo S, Chikamatsu K, Ohno T, Nakano T
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Journal Title
Cancer Science
Volume: 108
Issue: 10
Pages: 2039-2044
DOI
Related Report
Peer Reviewed / Open Access
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