Elucidation of the molecular mechanisms that define therapeutic responsiveness to immune checkpoint inhibitors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: The University of Tokyo
• Principal Investigator: Amemiya Takahiro 東京大学, 医学部附属病院, 助教 (20778617)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: がん / 免疫チェックポイント阻害剤 / 治療応答性 / 個別化医療

Outline of Final Research Achievements

We recently identified IL1RAP, a protein found to be altered during Lewis lung carcinoma (LLC) growth, correlates with therapeutic responsiveness to immune checkpoint inhibitors. We conducted a clinical study in patients treated with immune checkpoint inhibitors and demonstrated that IL-1 signaling pathway molecules are involved in therapeutic responsiveness to immune checkpoint inhibitors in this study. In addition, we found that adrenomedullin, whose expression is increased in LLC, decreased the expression of IL1RAP. Further continued studies will be conducted to identify molecular mechanisms.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤の開発により、複数のがん種において治療成績は大きく向上してきているが、治療応答性の良好な群と不良な群に分かれることが問題となっており、その解明が急務である。本研究によって、IL-1シグナル伝達経路分子が免疫チェックポイント阻害剤に対する治療応答性に関与している可能性が示された。今後、その作用メカニズムを明らかにすることで、治療成績の向上に繋がる可能性が期待される。