基于单细胞转录组学的新辅助免疫联合化疗治疗后肺鳞癌患者肿瘤免疫微环境特征的初步分析
Preliminary Analysis of Tumor Immune Microenvironment Characteristics in Lung Squamous Cell Carcinoma after Neoadjuvant Immunochemotherapy Based on Single-cell Transcriptomics
摘要
Abstract
Background and objective Neoadjuvant immunochemotherapy has emerged as an important treat-ment strategy for non-small cell lung cancer(NSCLC);however,substantial heterogeneity in therapeutic response persists among patients.Currently,treatment efficacy is primarily evaluated by imaging modalities,and there remains a lack of com-prehensive studies investigating post-treatment alterations in the tumor microenvironment(TME)and their association with clinical response.This study applied single-cell RNA sequencing(scRNA-seq)to characterize TME remodeling in lung squamous cell carcinoma after neoadjuvant immunochemotherapy and to explore its potential association with differences in therapeutic response.Methods Tumor specimens from two patients with lung squamous cell carcinoma who underwent surgical resection following neoadjuvant immunochemotherapy were subjected to scRNA-seq.An integrated analysis was per-formed to characterize the cellular composition,functional states,and intercellular communication patterns within the TME.Results Preoperative imaging evaluation indicated partial response(PR)in patient 1 and stable disease(SD)in patient 2,whereas postoperative pathological evaluation showed major pathological response(MPR)and partial pathological response(PPR),respectively.ScRNA-seq identified nine major cell populations.The TME exhibited marked heterogeneity between the two patients:patient 1 was characterized by immune cell enrichment and inflammatory activation,whereas patient 2 showed remodeling dominated by myeloid and endothelial signals,together with more prominent immune regulatory and angiogenic features.Cell-cell communication analysis revealed that patient 1 was mainly characterized by inflammatory chemotactic inter-actions,whereas patient 2 showed enhanced C-X-C motif chemokine ligand(CXCL),secreted phosphoprotein 1(SPP1),vascular endothelial growth factor(VEGF),macrophage migration inhibitory factor(MIF)and tumor necrosis factor(TNF)signaling,along with prominent immunosuppressive interaction axes.In addition,patient 2 showed a relative enrichment of macrophages and a more pronounced exhausted T-cell phenotype.Conclusion After neoadjuvant immunochemotherapy,the TME in pa-tients with lung squamous cell carcinoma exhibits marked heterogeneity in terms of cellular composition,functional states,and intercellular communication.The TME remodeling patterns revealed by scRNA-seq may provide insights into discrepancies in treatment response evaluation and help identify potential biomarkers.关键词
肺肿瘤/单细胞测序/新辅助治疗/肿瘤微环境Key words
Lung neoplasms/Single-cell sequencing/Neoadjuvant therapy/Tumor microenvironment引用本文复制引用
汪冠男,刘红雨,陈军,王亚楠,刘京豪,刘明辉,李宣广,张子禾,张洪兵,华钰,李永文..基于单细胞转录组学的新辅助免疫联合化疗治疗后肺鳞癌患者肿瘤免疫微环境特征的初步分析[J].中国肺癌杂志,2026,29(3):168-179,12.基金项目
本研究受国家科技重大专项(No.2025ZD0544700)、国家自然科学基金项目(No.82473191)、天津市重点医学学科建设项目(No.TJYXZDXK-3-002B,No.TJYXZDXK-3-006A-2)、天津市自然科学基金项目(No.23JCZDJC00710,No.24JCYBJC00330,No.23JCYBJC01010,No.25JCLZIC00230)以及国家高水平医院临床研究经费项目(No.LC2024L01)资助 This paper was supported by the grants from National Science and Technology Major Project(No.2025ZD0544700,to Jun CHEN),National Natural Science Foundation of China(No.82473191,to Jun CHEN),Tianjin Key Medical Discipline Construction Project(No.TJYXZDXK-3-002B,to Jun CHEN （No.2025ZD0544700）
No.TJYXZDXK-3-006A-2,to Jun CHEN),Natural Science Foundation of Tianjin(No.23JCZDJC00710,to Jun CHEN （）
No.24JCYBJC00330,to Hongyu LIU （）
No.23JCYBJC01010,to Yongwen LI （）
No.25JCLZIC00230,to Hongbing ZHANG)and National High Level Hospital Clinical Research Funding(No.LC2024L01,to Hongyu LIU). （No.LC2024L01,to Hongyu LIU）
