Immunoregulatory mechanisms in patients with LC-HCC

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08020
• 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: National Center for Global Health and Medicine
• Principal Investigator: Sachiyo Yoshio 国立研究開発法人国立国際医療研究センター, その他部局等, 室長 (10774060)
• Co-Investigator(Kenkyū-buntansha): 岡本 徹 大阪大学, 高等共創研究院, 教授 (80628595)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ナチュラルキラー細胞 / 肝臓癌

Outline of Final Research Achievements

Natural killer (NK) cells play a pivotal role in immune surveillance in the liver. We aimed to identify potential targets for NK cell-mediated immune intervention by revealing the functional molecules on NK cells in HCC patients. ILT2-positive CD56dim NK cells were increased in HCC patients compared with healthy volunteers. In HCC patients, ILT2-positive CD56dim NK cells were increased in cancerous IHLs compared with non-cancerous IHLs and PBMCs. The enhanced expression of ILT2 on CD56dim NK cells from HCC patients was inhibited by masking antibodies against MIF and CXCR4. ILT2-positive CD56dim NK cells exhibited lower capacities for cytotoxicity and ADCC than ILT2-negative cells, which were partially restored by ILT2 blockade. In HCC patients, ILT2 is a signature molecule for cancerous CD56dim NK cells with impaired cytolytic capacity. The MIF-CXCR4 interaction is associated with ILT2 induction on CD56dim NK cells and ILT2 serves as a target for functional NK cell restoration.

Free Research Field

肝臓免疫

Academic Significance and Societal Importance of the Research Achievements

切除不能肝癌の全身治療は免疫チェックポイント阻害薬の登場により、近年目覚ましい進歩を遂げていますが、治療無効症例および副作用により治療を継続できない症例も存在します。新規治療薬の探索は肝硬変合併肝癌患者さんの予後改善に重要であり、本研究成果がその一助となることが期待されます。