Elucidation and development of control method of the immune escape mechanism of circulating tumor cells of hepatocellular carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Hiroshima University
• Principal Investigator: Kobayashi Tsuyoshi 広島大学, 医系科学研究科(医), 准教授 (50528007)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 肝細胞癌 / 循環腫瘍細胞 / 遺伝子多型 / 免疫逃避機構

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.

Free Research Field

肝胆膵外科

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。