2022 Fiscal Year Final Research Report
Investigation of tumor immune escape mechanisms in liver cancer using allograft mouse model
| Project/Area Number |
20K08276
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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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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
金山 健剛 千葉大学, 医学部附属病院, 医員 (20835102)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 腫瘍微小環境 |
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| Outline of Final Research Achievements |
The antitumor effect of UNC1999, an EZH2 inhibitor, was clearly attenuated in an allogeneic mouse model compared to an immunodeficient mouse model. Flow cytometric analysis of H22 cell-derived tumors in BALB/c mice showed a significant decrease in interferon gamma+ CD8+ T cells and regulatory T cells and a significant increase in myeloid-derived suppressor cells (MDSCs). Combination of UNC1999 with Gr-1 neutralizing antibody restored the antitumor effect with an increase in the number of CD8+ T cells and a decrease in the number of MDSCs.
In conclusion, EZH2 inhibition contributes to attenuation of tumor immunity, and combination therapy with EZH2 inhibitors and agents that reduce MDSCs may be a novel therapeutic strategy for hepatocellular carcinoma.
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| Free Research Field |
分子腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
ポリコームタンパクEZH2は肝細胞がんにおいて高発現しており、発癌並びに癌の進行に大きな役割を果たすことが知られている。本研究では、同種移植マウスモデルにEZH2阻害剤を投与することで、EZH2の肝癌微小環境に与える影響を詳細に検証する事ができた。本研究成果は、癌免疫療法の新規アプローチの分子基盤の提供を可能とするものであり、学術的意義も富むものと考えられる。
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