Elucidation of HCC immune exhaustion system and establishment of treatment methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07890
• 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: Kanazawa University
• Principal Investigator: Okada Hikari 金沢大学, 医薬保健学総合研究科, 特任准教授 (50788916)
• Co-Investigator(Kenkyū-buntansha): 山下 太郎 金沢大学, 医学系, 教授 (90377432)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝細胞癌 / 腫瘍免疫

Outline of Final Research Achievements

Immune subclasses of liver cancer are also attracting attention as subtypes that are effective against immune checkpoint inhibitors (ICIs), but it is unclear whether they show clinical responses to ICIs. The applicant will determine whether an ICI-induced immune response occurs against liver cancer cells stratified according to the malignancy of the cancer and investigate the state of failure of the immune system in the tumor microenvironment to determine the causes of resistance to ICI responses. We identified the gene soluble form ST2 (sST2). Soluble form ST2 (sST2) promoted tumor growth by dysfunctioning cytotoxic CD8 T cells (CTLs), which are important in antitumor immunity.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

ST2陽性肝細胞癌の腫瘍内浸潤リンパ球における疲弊システムは解明されていない。本研究の成果は、申請者が新たに樹立した肝細胞癌株を用いてsST2陽性肝細胞癌の免疫非応答・疲弊機序を解明し、微小環境の免疫活性システムを正常化させる治療法に貢献することができた。申請者が作製したマウス新規肝細胞癌株は、完全にオリジナルでありヒト免疫学的分類に沿った基礎的研究が可能になり、癌免疫研究への発展に貢献できる。