Overcoming immune-related adverse events (irAE) induced by immune checkpoint inhibitors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07741
• 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: Hyogo University of Health Sciences
• Principal Investigator: Ohno Yoshiya 兵庫医療大学, 薬学部, 講師 (40509155)
• Co-Investigator(Kenkyū-buntansha): 田中 稔之 兵庫医療大学, 薬学部, 教授 (30217054)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫関連有害事象 / 免疫チェックポイント阻害薬 / IL-18 / 肝傷害

Outline of Final Research Achievements

Immune checkpoint inhibitors (ICIs) strongly induce an immune response against tumor, but they also release the immune response against the self, resulting in tissue injury (immune-related adverse events, irAEs). However, the mechanisms of irAEs remain unclear. We generated an irAE mouse model in which liver injury is induced by ICI, and found that ICI-induced liver injury is an autoinflammatory tissue destruction associated with inflammatory cell infiltration, and that IL-18 may be involved in anti-inflammation via innate lymphocytes in the liver.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害薬による免疫療法の拡大に伴って作用である免疫関連有害事象の報告が増加し、その機序の解明と克服が急がれる。免疫関連有害事象の機序の解明は、免疫療法の安全性をもたらし、大きな社会的・医学的意義を持つ。また、IL-18による正常組織保護作用を明らかにすることは、新たな治療標的を開拓し、IL-18を中心とした新しい学術分野の創造が期待されるなど大きな学術的意義を持つ。