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分子和免疫特征与转移性NSCLC患者的长期益处相关,这些患者接受了免疫检查点阻塞

Pedro Rocha^1,2, Rafael Bach¹, Laura Masfarré¹

¹Medical Oncology Department, Hospital del Mar, Barcelona, Spain.

|February 24, 2025

概括

在转移性非小细胞肺癌 (NSCLC) 免疫检查点阻塞 (ICB) 中,确定长期益处的生物标志物至关重要. 预先存在的抗瘤免疫,由特定蛋白质和免疫细胞标记物表明,预测NSCLC患者对ICB的长期反应.

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.
蛋白质组学是指蛋白质组学.

背景情况:

免疫检查点阻塞 (ICB) 在各种固体瘤中提供了显著的好处,包括转移性非小细胞肺癌 (NSCLC).
然而,预测长期对ICB反应的可靠生物标志物仍然难以捉摸,阻碍了最佳治疗选择.

研究的目的:

确定与长期反应 (LTR) 与转移性NSCLC中ICB的短期反应 (STR) 相关的临床病理学,基因组和蛋白质组特征.
探索潜在的生物标志物来预测ICB治疗的长期益处.

主要方法:

对49名转移性NSCLC患者进行ICB治疗的分析,将响应者分为LTR (>24个月) 和STR (<6个月).
在瘤组织上进行了血ctDNA下一代测序 (NGS),血清蛋白质组学和GeoMx数字空间分析 (DSP).
在治疗前和治疗初期收集了纵向血液样本.

主要成果:

LTR患者表现出更高的PD-L1表达和免疫相关不良事件 (irAEs) 的发生率.
基因组分析显示,同时发生的KRAS/STK11和TP53/KMT2D突变与缺乏ICB益处有关.
在LTR患者中,基线血清蛋白质组学和空间分析确定了免疫相关蛋白质 (例如,细胞亡,化学反应,MHC I 类处理,免疫恒常标志物) 和免疫细胞透 (CD45,CD8,HLA-DR) 的水平升高.

结论:

多模式分析确定了临床病理学和免疫学特征,预测了长期ICB在转移性NSCLC中的益处.
预先存在的抗瘤免疫的存在是长期反应的强有力的预测指标.
这些发现提供了对潜在生物标志物和提高ICB在NSCLC疗效的策略的见解.

关键词:

基于血液的生物标志物免疫治疗是一种免疫疗法.数字空间概况设计的数字空间概况.长期响应者长期响应者肺部瘤是什么肺部瘤血清蛋白质组的血清蛋白质组是

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