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蛋白激酶Cι驱动的巨细胞透介导非小细胞肺癌中的免疫抑制

Shichuan Hu¹, Zichen Zhao², Jing Zhao³

¹Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

|February 20, 2026

概括

蛋白激酶Cι (PKCι) 驱动非小细胞肺癌 (NSCLC) 免疫治疗的耐药性. 用奥拉诺芬抑制PKCι通过减少免疫抑制细胞和促进T细胞反应来增强抗PD-1疗法.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

非小细胞肺癌 (NSCLC) 是癌症死亡的主要原因.
针对PD-1/PD-L1轴的免疫检查点抑制剂 (ICI) 在NSCLC患者的一个子集中显示出有效性,但耐药性很常见.
识别ICI耐药性的机制对于改善治疗结果至关重要.

研究的目的:

在NSCLC中识别抗PD-1 (αPD1) 治疗耐药性的生物标志物和媒介.
阐明PKC介导的ICI耐药性背后的分子机制.
评估与αPD1疗法结合抑制PKCι的治疗潜力.

主要方法:

在NSCLC患者中,PKCι表达与αPD1治疗反应的相关分析.
研究PKCι在调节瘤微环境组件中的作用,包括瘤相关巨细胞 (TAM) 和CD8+ T细胞.
在临床前NSCLC模型中使用auranofin (AF) 抑制PKCι的药理抑制.
对AF和αPD1联合治疗对瘤生长和免疫反应的评估.

主要成果:

高PKCι表达与对αPD1治疗的耐药性相关,而低表达表明敏感性.
PKCι通过Yap1通路调节CCL7,促进免疫抑制性瘤微环境,导致TAM增加和CD8+T细胞减少.
用奥拉诺芬制止PKCι的药理抑制降低了TAMs,增强了CD8+T细胞的透,并与αPD1疗法协同控制瘤生长.

结论:

在NSCLC中,PKCι是PD-1阻塞抵抗的关键调解者和生物标志物.
PKCι-Yap1-CCL7轴促进免疫抑制性瘤微环境,驱动ICI耐药性.
抑制PKCι是一种有前途的治疗策略,可以克服ICI耐药性,并提高NSCLC的免疫疗法疗效.

关键词:

免疫疗法耐药性免疫疗法耐药性非小细胞肺癌是非小细胞肺癌.PKCι PKCι 是一个小镇.与瘤相关的巨细胞.

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