Development of Immunotherapy Utilizing the Adenosine Pathway in EGFR-Mutant Lung Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15503
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Yoshida Ryohei 旭川医科大学, 医学部, 客員助教 (40792883)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: EGFR肺がん / アデノシン経路

Outline of Final Research Achievements

The significance of CD26, part of the adenosine pathway, has been identified in the context of Immune checkpoint inhibitor (ICI) resistance in EGFR-mutant lung cancer (EGFR lung cancer). In the EGFR lung cancer cell line HCC2279, cells with low CD26 expression (CD26-Low) exhibited high STING expression, suggesting a potential enhancement of immune response. Furthermore, knocking out STING in CD26-Low cells led to a significant increase in CD26 expression, indicating that the cGAS-STING pathway negatively regulates CD26 expression. These findings suggest that suppressing CD26 expression in EGFR lung cancer could lead to the development of new immunotherapies.

Free Research Field

肺がん

Academic Significance and Societal Importance of the Research Achievements

本研究は、EGFR肺がんにおけるICIs抵抗性のメカニズム解明に寄与し、特にCD26とcGAS-STING経路の関与を示した点で学術的に重要である。これにより、CD26の発現を低下させることで免疫応答を高める新たな治療戦略が提案できる。また、EGFR遺伝子変異陽性肺がん患者に対する治療の選択肢が増えることで、治療効果の向上と副作用の軽減が期待され、社会的意義も大きい。これらの知見は、今後の新規免疫療法の開発に向けた基盤となる。