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Updated: Jul 23, 2025

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在未经治疗的高级非小细胞肺癌中,HLA-I进化分歧对PD-1阻塞加上化疗产生反应

Tao Jiang¹, Qiqi Jin^2,3,4, Jiahao Wang^2,4

¹Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Clinical cancer research : an official journal of the American Association for Cancer Research

|July 14, 2023

概括

高HLA类I进化分歧 (HED) 预测在接受PD-1阻断加化疗的高级非小细胞肺癌 (NSCLC) 患者的生存率有所改善. 这种生物标志物增强了治疗反应,并表明瘤微环境更加炎症.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
遗传学遗传学是一个

背景情况:

PD-1阻塞加化疗是高级非小细胞肺癌 (NSCLC) 的标准治疗方法.
对于这种治疗组合,仍需要预测性生物标志物.

研究的目的:

为了研究HLA类I进化分歧 (HED) 的预测和预后价值,在接受一线PD-1阻断加化疗治疗的NSCLC患者中.
探索HED和瘤微环境特征之间的关联.

主要方法:

在两个III期试验 (CameL和CameL-sq) 中,来自427名NSCLC患者的综合临床,基因组和生存数据.
分析了HLA类I进化分歧 (HED) 作为预测生物标志物.
利用多变量分析,调整PD-L1表达和瘤突变负担.
在11名患者的样本上进行单细胞RNA测序.

主要成果:

在接受PD-1阻塞加化疗,但不仅仅是化疗的患者中,高HED显著预测了改善的客观响应率 (ORR),无进展生存率 (PFS) 和整体生存率 (OS).
高HED独立地与更好的ORR,PFS和OS有关,即使在调整PD-L1和瘤突变负担之后.
结合HED和PD-L1表达,与单独的生物标志物相比,其预测性表现优越.
具有高HED的瘤表现出增强的抗原呈现和T细胞介导免疫力,这表明瘤微环境炎症.

结论:

高HED是一种有前途的生物标志物,用于预测先进NSCLC患者的生存益处,这些患者接受一线PD-1阻断加化疗治疗.
HED可能表明炎症瘤微环境有利于免疫疗法反应.

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