The analysis of HCC immune microenvironment after receiving various kinds of HCC treatments for the improvement of iCI treatments

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kumamoto University (2020-2021); Nagoya City University (2019)
• Principal Investigator: Kondo Yasuteru 熊本大学, 大学院生命科学研究部(医), 客員准教授 (70455822)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Tregs / PD-1 / iCIs / MDSCs

Outline of Final Research Achievements

We could find that the expression of FoxP3 was significantly decreased after the treatment of sorafenib by using deep-sequencing analysis and PBMCs from HCC patients. Then, we carried out immune subsets analysis by using multi-color FACS. We could find that Tregs and MDSCs were significantly decreased after the treatment of sorafenib and Th1 cells was significantly increased after the treatment of sorafenib. Moreover, we demonstrated that the pre-existing ANA and characteristic liver histology including CD8+ cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis by anti-PD-1 therapy.

Free Research Field

肝臓内科学

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌に対して代表的なTKIであるSorafenibを使用した際にiCIs治療の効果が増強しうる免疫環境に変化することがわかった。現在、様々なiCIs治療のコンビネーションやSequential治療が試みられているが、その際の治療判断の一助になると思われる。また、iCIs治療を行なった際の肝障害に特徴的な肝病理学的組織像も明らかとなったため、早期にステロイド投与の要否の判断が可能となり、より安全にiCIs治療が行えるようになると思われる。