单细胞图谱揭示了抗PD-1治疗的非小细胞肺癌的免疫异质性，这一成果由北京大学生命科学学院张泽民研究组经过不懈努力而取得。2025年3月26日，国际知名学术期刊《细胞》发表了这一成果。
课题组应用单细胞RNA和TCR测序（scRNA/TCR-seq）分析了234例新辅助化疗免疫治疗后的非小细胞肺癌手术肿瘤样本。分析显示五种不同的TIME亚型具有不同的主要病理反应（MPR）率。MPR患者FGFBP2+ NK/NK样T细胞、记忆B细胞或效应T细胞水平升高，而非MPR患者CCR8+ Tregs水平升高。T细胞克隆扩增分析揭示了非mpr患者的异质性，其特征是tex相关细胞和CCR8+ Tregs扩增量不同。前体衰竭T细胞（Texp细胞）与无复发生存率相关，确定了尽管缺乏MPR，但复发风险降低的患者亚组。他们的研究剖析了对化疗免疫治疗反应的TIME异质性，为非小细胞肺癌的管理提供了见解。
据了解，抗PD-(L)1治疗是非小细胞肺癌（NSCLC）的标准治疗，但患者对同一方案的反应不同。肿瘤免疫微环境（TIME）与免疫治疗反应相关，但治疗结果的异质性仍未得到充分探讨。
附：英文原文
Title: A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer
Author: Zedao Liu, Zhenlin Yang, Junqi Wu, Wenjie Zhang, Yuxuan Sun, Chao Zhang, Guangyu Bai, Li Yang, Hongtao Fan, Yawen Chen, Lei Zhang, Benyuan Jiang, Xiaoyan Liu, Xiaoshi Ma, Wei Tang, Chang Liu, Yang Qu, Lixu Yan, Deping Zhao, Yilong Wu, Shun He, Long Xu, Lishan Peng, Xiaowei Chen, Bolun Zhou, Liang Zhao, Zhangyi Zhao, Fengwei Tan, Wanting Zhang, Dingcheng Yi, Xiangjie Li, Qianqian Gao, Guangjian Zhang, Yongjie Wang, Minglei Yang, Honghao Fu, Yongjun Guo, Xueda Hu, Qingyuan Cai, Lu Qi, Yufei Bo, Hui Peng, Zhigang Tian, Yunlang She, Chang Zou, Linnan Zhu, Sijin Cheng, Yi Zhang, Wenzhao Zhong, Chang Chen, Shugeng Gao, Zemin Zhang
Issue&Volume: 2025-03-26
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.
DOI: 10.1016/j.cell.2025.03.018
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00291-0