Liver pathology of immune-related adverse events

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kanazawa University
• Principal Investigator: Harada Kenichi 金沢大学, 医学系, 教授 (30283112)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肝臓 / 病理 / 免疫チェックポイント阻害剤 / 免疫関連有害事象

Outline of Final Research Achievements

Pathological investigation of the pathogenesis of immune checkpoint inhibitor-associated immune-related adverse events (irAE) liver injury revealed the histological diversity and characteristics of iAE liver injury and its histology is distinct from drug-induced liver injury and autoimmune hepatitis. Indoleamine 2,3-dioxygenase-1 (IDO-1), initially found as a biomarker for primary biliary cholangitis, was expressed in interlobular bile ducts of irAE liver injury as well as those of primary biliary cholangitis. Although there is little histological similarity of bile duct lesions between these diseases, the presence of commonalities in the development of bile duct lesions based on the IFNγ milieu around the bile ducts was suggested.

Free Research Field

病理

Academic Significance and Societal Importance of the Research Achievements

がん患者に対する免疫チェックポイント阻害薬治療の普及にともない免疫関連有害事象肝障害症例も増加しつつあるが、実臨床では免疫チェックポイント阻害剤による肝障害なのか、その他の抗がん剤等による肝障害なのか鑑別が困難なことが多い。今回の研究成果は、免疫関連有害事象関連肝胆道系障害の病態解明のみならず診断にも応用可能であり、免疫チェックポイント阻害薬治療への更なる普及と迅速な治療介入への指針として重要な内容といえる。