| Project/Area Number |
18K15196
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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 49070:Immunology-related
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| Research Institution | Toyama Prefectural University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | エピジェネティクス / がん免疫 / Treg / PD-L1 / 制御性T細胞 |
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| Outline of Final Research Achievements |
Antibody-based drug is widely used for cancer immunotherapy; however, the high cost of this type of drug is problem to be solved. In this study, We focused on small molecule inhibitor against histone deacetylase (HDAC) that regulates epigenetic modification and evaluated the effect of HDAC inhibitors on cancer immunotherapy. Among several HDAC isozyme specific inhibitors, we found HDAC inhibitor B suppressed the differentiation of naive T cells into regulatory T cells. The reduction of regulatory cells and anti-tumor effect of this inhibitor were also observed even in <i>in vivo</i> HDAC knockout tumor model, indicating that the HDAC inhibitor might show anti-tumor effect through the modification of immune function . In addition, this inhibitor suppressed PD-L1 expression in cancer cells. Collectively, HDAC inhibitor B may be potent immune regulator that enhance anti-tumor immunity.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性腫瘍に対する治療法として、近年抗体医薬品を用いたがん免疫療法が開発され、臨床で良好な成績を収めている。一方、抗体医薬品は従来の低分子化合物をベースとした薬剤と比較して薬価が著しく高く、患者のQOLの低下や医療費の圧迫が懸念されている。本研究ではエピジェネティクス機構を標的とした低分子化合物が、がん免疫療法の標的となる分子の発現を阻害することや、がん免疫の抑制を担うヘルパーT細胞サブセットの分化を抑制することを見出した。この知見を発展させ、低分子化合物をベースとした新たながん免疫療法の薬を開発することができれば、近年の抗体医薬品の薬価の問題をカバーできると期待できる。
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