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非小細胞肺がんにおける免疫療法耐性:メカニズムから治療の機会まで

Huiyu Wang^1,2, Xiaomin Niu^3,4, Zhenning Jin^1,2

¹Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, 314006, China.

Journal of experimental & clinical cancer research : CR

|August 24, 2025

まとめ

非小細胞肺がん (NSCLC) の免疫療法耐性を理解することは極めて重要です. このレビューでは,耐性のメカニズムと,よりよい患者のアウトカムのために免疫チェックポイント阻害剤 (ICI) の有効性を改善する戦略を詳細に述べています.

科学分野:

腫瘍学
免疫学
癌研究

背景:

非小細胞肺がん (NSCLC) は,世界中でがんによる死亡の主な原因です.
免疫チェックポイント阻害剤 (ICI) は,一部の進行NSCLC患者の生存率を改善します.
NSCLCの70%以上がICIに耐性を発症し,耐性メカニズムの研究が求められます.

研究の目的:

NSCLCにおける免疫療法耐性に関する現在の知識を統合する.
免疫脱出に寄与する内在的および外在的要因を分析する.
抵抗を克服するための治療戦略を議論する.

主な方法:

臨床前モデルと臨床試験に関する包括的な文献レビュー
抵抗メカニズムを腫瘍内および腫瘍外プロセスに分類する.
抗原表現,腫瘍微環境 (TME),微生物群を含む要因の分析.

主要な成果:

抵抗は,腫瘍抗原の喪失,抗原表現の障害,cGAS-STING経路の異常,TMEの代謝再プログラム,免疫細胞の疲労,および微生物体の変化を含む.
肺と腸の微生物は,抗生物質とメタボリットの生成を通して免疫療法反応に影響します.
併用療法 (化学療法,放射線療法,抗血管新生剤,表遺伝子調節剤) と新薬 (双特定抗体,ADC) が有望である.

結論:

バイオマーカーによる分層化と結合免疫療法は,応答の持続性を改善するために不可欠です.
腫瘍の免疫原性を回復し,TME抑制に取り組むことが重要です.
NSCLCのパーソナライズされた免疫療法の進歩には,多角的なアプローチが不可欠です.

キーワード:

併用療法 ICI について免疫抵抗性免疫療法肺がん

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