翁凯 (2025-04-03 20:39):
#paper 【doi】10.1016/j.cell.2025.03.018;【发表年份】2025年;【期刊】Cell;【标题】A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer。本研究的目标是探究非小细胞肺癌(NSCLC)患者在接受抗PD-1治疗后的免疫微环境异质性,以了解不同患者对治疗反应的差异。研究者们通过单细胞RNA测序(scRNA-seq)和T细胞受体测序(scTCR-seq)分析了234名接受新辅助化疗联合抗PD-1治疗的NSCLC患者的肿瘤样本。研究发现,这些患者可以分为五种不同的肿瘤免疫微环境(TIME)亚型,这些亚型与主要病理反应(MPR)率相关。具体来说,NK细胞、记忆B细胞和耗竭前体T细胞与MPR相关,而非MPR患者则表现出更高的CCR8+ Tregs水平。此外,T细胞克隆扩增特征分析揭示了非MPR患者中的异质性,表现为Tex相关细胞和CCR8+ Tregs的不同扩增程度。研究还发现,耗竭前体T细胞(Texp细胞)的比例与无复发生存期相关,能够识别出尽管未达到MPR但复发风险降低的患者亚组。这项研究提供了对化疗免疫治疗反应的TIME异质性分析,为NSCLC管理提供了新的见解。
IF:45.500Q1 Cell, 2025-3. DOI: 10.1016/j.cell.2025.03.018 PMID: 40147443
A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer
翻译
Abstract:
Anti-PD-(L)1 treatment is standard for non-small cell lung cancer (NSCLC), but patients show variable responses to the same regimen. The tumor immune microenvironment (TIME) is associated with immunotherapy response, yet the heterogeneous underlying therapeutic outcomes remain underexplored. We applied single-cell RNA and TCR sequencing (scRNA/TCR-seq) to analyze surgical tumor samples from 234 NSCLC patients post-neoadjuvant chemo-immunotherapy. Analyses revealed five distinct TIME subtypes with varying major pathological response (MPR) rates. MPR patients had elevated levels of FGFBP2 NK/NK-like T cells, memory B cells, or effector T cells, while non-MPR patients showed higher CCR8 Tregs. T cell clonal expansion analyses unveiled heterogeneity in non-MPR patients, marked by varying expansions of Tex-relevant cells and CCR8 Tregs. Precursor exhausted T cells (Texp cells) correlated with recurrence-free survival, identifying a patient subgroup with reduced recurrence risk despite lack of MPR. Our study dissects TIME heterogeneity in response to chemoimmunotherapy, offering insights for NSCLC management.
翻译
回到顶部