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定义非小细胞肺癌瘤微环境变化在原发性和获得性免疫检查点抑制剂抵抗使用临床和现实世界的数据

Lang Ho Lee¹, Xin Xu¹, Thanos Mourikis²

¹Novartis Pharmaceuticals Corporation, Cambridge, Massachusetts.

Cancer research communications

|June 9, 2025

概括

在非小细胞肺癌 (NSCLC) 中免疫检查点抑制剂 (ICI) 耐药性在原发性和获得性状态之间有所不同. 获得性耐药性显示出更高的IFNγ和T细胞枯竭,而初级耐药性则具有较低的B细胞和树突细胞表达,指导新的疗法.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
基因组学就是基因组学.

背景情况:

免疫检查点抑制剂 (ICI) 对非小细胞肺癌 (NSCLC) 有效.
初级和获得ICI耐药性的瘤微环境 (TME) 变化未得到充分研究.
在疾病进展时采集组织活检具有挑战性.

研究的目的:

在先进阶段的NSCLC中研究TME在原发性与获得ICI耐药性的差异.
确定潜在的生物标志物和治疗目标,以克服ICI耐药性.

主要方法:

从三个NSCLC队列 (Tempus,CANOPY-1,SU2C) 中利用了临床和现实世界的数据.
分析了治疗结果信息和组织RNA测序数据.
在初级电阻和获得电阻状态下比较TME特征.

主要成果:

获得性耐药性与更高的IFNγ和T细胞耗尽有关.
主要耐药性表现出较低的B细胞和树突细胞表达,可能是由于之前的基于的化疗.
基线转录组学表明先天性免疫细胞在PD-L1<1%的NSCLC中很重要,而IFNγ和T细胞炎症预测PD-L1≥1%的NSCLC的结果.

结论:

在初级ICI耐药性和获得ICI耐药性之间观察到TME的显著差异.
骨髓状细胞可能在PD-L1<1%的NSCLC群体中的ICI耐药性中发挥关键作用.
这些发现为开发下一代疗法以克服ICI耐药性提供了洞察力.

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