Molecular mechanisms underlying differentiation/mobilization of tumor-associated macrophages by cancer-associated fibroblasts.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16372
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Juntendo University (2022-2023); National Cancer Center Japan (2020-2021)
• Principal Investigator: Suzuki Jun 順天堂大学, 医学部, 助教 (80869933)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: がん関連線維芽細胞 / 腫瘍関連マクロファージ / 腫瘍微小環境

Outline of Final Research Achievements

In non-small cell lung cancer, cancer-associated fibroblasts (CAFs) have been shown to correlate with the accumulation of tumor-promoting tumor-associated macrophages (TAMs). Specifically, CAFs exhibiting a podoplanin-positive phenotype demonstrated enhanced expression of cytokine genes involved in creating an immunosuppressive tumor microenvironment. This suggests that CAFs influence TAMs through some pathway, contributing to the formation of an immunosuppressive and tumor-promoting immune microenvironment. Our report suggests the involvement of TGF-β. Establishing an experimental system to differentiate monocytes into macrophages and elucidating the detailed mechanisms of interaction between CAFs and TAMs is a future challenge.

Free Research Field

腫瘍微小環境

Academic Significance and Societal Importance of the Research Achievements

非小細胞肺がん（NSCLC）の免疫微小環境（IME）を研究することは、治療法の開発と予後の改善において極めて重要である。免疫チェックポイント阻害剤のような新たな免疫療法の効果を予測・最適化するためには、IMEの詳細な理解が不可欠である。我々は腫瘍間質に着目し、がん関連線維芽細胞と腫瘍関連マクロファージの関係性を明らかにした。今後さらなる詳細なメカニズムを含むIMEの特性を解明することで、新たなバイオマーカーの発見や、個別化医療の推進が期待されると考えている。