Earliest HLA-bound endocrine biomarkers in immune checkpoint inhibitor therapy.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17541
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Wakayama Medical University
• Principal Investigator: KURIMOTO CHIAKI 和歌山県立医科大学, 医学部, 助教 (90751040)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 免疫チェックポイント阻害薬

Outline of Final Research Achievements

We have explored immune-checkpoint inhibitors induced ‘immune-related adverse events’ in endocrine organs (endocrine IRAE). The study was aimed to identify HLA-restricted epitope in earliest phase and to diagnose/manage endocrine IRAE. We have discovered predispose HLA to thyroid IRAE, and reported cytokine/chemokine alteration with thyroid damage. Moreover, we have found that certain chemical factors and host factors are associated with development of type 1 diabetes by immune-checkpoint inhibitors as pancreatic IRAE. Taken, comprehensive examination among multiple endocrine organs seemed to be important in the future studies.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤は、がん免疫療法に用いられる新規薬剤である。免疫チェックポイント阻害剤治療の際に5割以上と高頻度に内分泌臓器における免疫関連有害事象（IRAE）が発症する。これまで、内分泌IRAEの障害臓器として下垂体、膵臓、甲状腺等が報告されてきた。しかし、内分泌IRAEの発症機序や、そのバイオマーカーは不明であった。本研究の目的は、超早期のHLA拘束性バイオマーカーを同定し、内分泌IRAEの早期診断治療につなげることである。