| Project/Area Number |
18K08706
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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 55020:Digestive surgery-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肝細胞癌 / 循環腫瘍細胞 / 遺伝子多型 / 免疫逃避機構 / SIRPα / CD47 / 免疫逃避 |
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| Outline of Final Research Achievements |
The purpose of this study was to elucidate and develop a method for releasing immune escape mechanism in the macrophage immune checkpoint system using single-cell analysis of Glypican-3 (GPC3) -positive circulating tumor cells (CTC) specific for hepatocellular carcinoma (HCC).
In a study of 132 HCC patients, GPC3-CTC, AFP, DCP, and multiple tumors were independent risk factors for postoperative recurrence. In the SIRPα IgV domain variant analysis of 255 HCC patients, V1 variant was significantly poor in both recurrence-free survival rate and overall survival rate. The effect of CD47 expression on GPC3-CTC on prognosis was not significant. In the analysis of PD-1 gene polymorphism PD-1.1 in 321 HCC patients, the GG allele had a significantly higher rate of extrahepatic recurrence.
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| Academic Significance and Societal Importance of the Research Achievements |
HCCの再発予防療法開発が困難な理由として、heterogeneityが極めて大きいことが考えられるが、HCC特異的なGPC3-CTCを標的とした機能解析や治療戦略はheterogeneityを克服できる可能性を秘めている。マクロファージCD47-SIRPαシグナルは新たな免疫チェックポイント機構であり、その阻害療法が期待されている。CD47-SIRPαシグナルにおける免疫回避機構解明とその制御法の開発は、画期的な治療手段となる可能性がある。
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