The role of B cell-activating factor for hepatocarcinogenesis induced by non-alcoholic steatohepatitis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16991
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Ehime University
• Principal Investigator: NAKAMURA Yoshiko 愛媛大学, 医学部附属病院, 助教 (40867256)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝癌 / 非アルコール性脂肪性肝炎 / B細胞活性化因子 / 微小環境

Outline of Final Research Achievements

In this study, the role of B cell-activating factor (BAFF) in fatty liver disease-induced hepatocarcinogenesis was analyzed using BAFF-knockout (BAFF-KO) mice. We established mouse model with steatosis and hepatocellular carcinoma by single intraperitoneal administration of Diethylnitrosamine (DEN) and feeding with high fat diet. Both of the number and the size of tumors were larger in the livers of BAFF-KO mice than in those of wild-type mice, in accordance with the results of PCNA-staining and gene expression related to cell cycles. Additionally, liver nonparenchymal cells analysis showed that BAFF-KO mice had significantly more percentages of myeloid-derived suppressor cells and regulatory T cells than wild-type mice. These findings suggest that BAFF may contribute to immunosuppressive cells functions and subsequent hepatocarcinogenesis in fatty liver disease.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

近年ウイルス性肝癌が減少傾向を示す一方で、耐糖能異常や脂質異常症など肥満関連代謝異常を合併した非アルコール性脂肪肝疾患を背景とする肝癌が全世界的に増加している。脂肪肝症例から発癌例を抽出すること並びにその治療戦略を確立する必要がある。また様々な癌種においてT細胞を標的とした免疫治療が標準治療の一つとなっているが、申請者はBAFFが脂肪性肝疾患における免疫異常と発癌を繋ぐ重要な因子の一つではないかと考えている。肝発癌のメカニズムと治療法の確立は重要であり、本研究成果は脂肪性肝疾患のみならず肥満関連疾患などの領域にも波及することが期待される。