Elucidating the relationship between autoantibodies and immune cell activation in immune-related adverse events induced by immune checkpoint inhibitors

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K07669
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Okinaka Memorial Institute for Medical Research
• Principal Investigator: Miura Yuji (財)冲中記念成人病研究所, その他部局等, 研究員 (10453698)
• Co-Investigator(Kenkyū-buntansha): 菰原 義弘 熊本大学, 大学院生命科学研究部(医), 教授 (40449921) ; 元島 崇信 熊本大学, 大学院生命科学研究部(医), 助教 (60726355) ; 田辺 裕子 (財)冲中記念成人病研究所, その他部局等, 研究員 (00743692)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 免疫関連有害事象 / 免疫チェックポイント阻害薬 / マクロファージ / バイオマーカー / CXCL10 / CD74 / 自己抗体

Outline of Final Research Achievements

This study aimed to elucidate the pathogenesis of immune-related adverse events (irAEs) and establish predictive biomarkers for their occurrence. Previous research has clarified the correlation between plasma anti-CD74 antibodies and irAE-related pneumonitis. Therefore, this study focused on elucidating the mechanism and replicating the findings in a Japanese cohort. While commercially available anti-CD74 antibodies showed macrophage activation, IgG from patients with irAEs did not exhibit such activity. Moreover, in the Japanese cohort, anti-CD74 autoantibodies did not correlate with the occurrence of irAE-related pneumonitis or irAEs in general. However, a comprehensive analysis of plasma cytokines and chemokines revealed a correlation between CXCL10 and irAE development. The results suggest that macrophages may be involved in the pathogenesis of irAEs, but further research is required.

Free Research Field

がん免疫

Academic Significance and Societal Importance of the Research Achievements

近年、免疫チェックポイント阻害薬の開発により、様々ながん種においてその予後が改善した。しかしながら、免疫関連有害事象（irAE）は時に致死的となり、実臨床の課題の一つである。そのため、発症機序の解明と発症予測バイオマーカーの開発が求められている。本研究では、マクロファージが発症機序に関わっている可能性と血漿CXCL10が発症予測につながる可能性を示唆した。