Construction of the foundation for the elucidation of the resistance mechanisms of the anti-PD-1 cancer therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19392
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Miyajima Michio 国立研究開発法人理化学研究所, 生命医科学研究センター, 客員研究員 (80586404)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: PD-1

Outline of Final Research Achievements

In this research project, we established a basis for analyzing the mechanism of PD-1 therapy resistance in cancer: we established an experimental system for in vivo non-biased screening of cancers that have acquired resistance to anti-tumor responses enhanced by PD-1 dysfunction, which is known to be eliminated upon inoculation into PD-1-deficient mice. One cell line was obtained from the parental cancer cells that would form tumors when inoculated into PD-1-deficient mice. This cell line was also resistant to administration of anti-PD-1 and anti-PD-L1 antibodies after inoculation into wild-type mice. Thus, a new cell line was established that enables analysis of the PD-1 therapy resistance mechanisms in cancer.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

がんのPD-1療法は幅広い適応で開発が進められているが近年耐性がんも報告されてきており、耐性がんの治療法開発への社会的要望は強くなっている。しかしながらがんのPD-1療法耐性メカニズムは不明な点が多く治療法開発の障壁となっている。
耐性メカニズムに不明な点が多い理由の1つは解析する実験系が乏しいことである。本研究課題によりがんの抗PD-1抗体療法耐性メカニズム解明に向けた新たな実験基盤が構築された。
本研究結果を基にPD-1療法耐性がんの治療法や治療効果予測マーカーの開発といった応用研究が発展し、その波及効果は医療界や産業界へも及ぶことが想定されるため本研究成果は意義深いものとなったと言える。