Fundamental research for the development of novel cancer immunotherapy by elucidating multicellular interactions in hepatocellular carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02899
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa University
• Principal Investigator: Mizukoshi Eishiro 金沢大学, 附属病院, 特任教授 (90345611)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: T細胞 / 肝細胞癌 / 単一細胞解析 / 免疫細胞プロファイル / 遺伝子改変T細胞 / T細胞レセプター / 免疫治療 / ペプチド

Outline of Final Research Achievements

Research was conducted to clarify factors affecting antigen-specific T cells in liver cancer, leading to the development of novel immunotherapy. The following results were obtained: 1) A method was established to generate genetically engineered T cells with antigen-specific T cell receptors (TCRs); 2) Single-cell gene expression analysis was performed using peripheral blood lymphocytes from patients with long-term survival, and molecules involved in immune memory and fatigue resistance of T cells with TCRs specific to hepatocellular carcinoma (HCC) were identified; 3) In a study on the interaction between T cells and other immune cells, we identified changes in the immune response of T cells to HCC that occur in the body after hepatitis C virus elimination.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

抗原特異的T細胞レセプター（TCR）を有する遺伝子改変T細胞の作製方法を確立したことにより、今後本技術を用いたT細胞輸注療法による免疫治療の開発が加速する。また、長期生存が得られたがん患者の腫瘍に特異的なT細胞の性質を規定する分子を同定したことにより、同分子を標的とした新規免疫治療の開発が可能となる。これらの治療開発により、肝がん患者の予後が改善できる可能性があるとともに、他の難治がんへの応用が期待される。