Liu Yu, Qin Denghui, Fu Jiejun
Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi, China.
Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, Nanning, Guangxi, China.
Front Immunol. 2025 May 29;16:1604310. doi: 10.3389/fimmu.2025.1604310. eCollection 2025.
Non-small cell lung cancer (NSCLC) immunotherapy has been revolutionized by immune checkpoint inhibitors (ICIs), yet response heterogeneity persists due to dynamic tumor-immune interactions. This review summarizes recent studies in understanding tumor-infiltrating lymphocyte (TIL) biology, highlighting CD8 cytotoxic T cells and regulatory T cells (Tregs) as pivotal regulators of immune surveillance and suppression. We summarize emerging biomarkers such as TCR clonality, spatial distribution of tumor-infiltrating lymphocytes (TILs), and exhaustion markers including PD-1, TCF1, and TIM-3, which predict immune checkpoint inhibitor (ICI) efficacy beyond PD-L1 expression. This review specifically describes radiotherapy-induced immunogenic remodeling and peripheral T cell dynamics as innovative strategies to monitor immune response and resistance mechanisms. By integrating results from single-cell omics and AI-driven spatial analysis, we propose multidimensional frameworks of TIL in NSCLC to overcome resistance and optimize immunotherapy combinations. These insights collectively advance NSCLC immunotherapy toward precision modulation of the tumor immune microenvironment.
免疫检查点抑制剂（ICI）彻底改变了非小细胞肺癌（NSCLC）的免疫治疗，但由于动态的肿瘤-免疫相互作用，反应异质性仍然存在。本综述总结了近期在理解肿瘤浸润淋巴细胞（TIL）生物学方面的研究，强调CD8细胞毒性T细胞和调节性T细胞（Tregs）是免疫监视和抑制的关键调节因子。我们总结了新兴的生物标志物，如TCR克隆性、肿瘤浸润淋巴细胞（TILs）的空间分布以及包括PD-1、TCF1和TIM-3在内的耗竭标志物，这些标志物可预测免疫检查点抑制剂（ICI）疗效，且不受PD-L1表达的影响。本综述特别描述了放疗诱导的免疫原性重塑和外周T细胞动态，作为监测免疫反应和耐药机制的创新策略。通过整合单细胞组学和人工智能驱动的空间分析结果，我们提出了NSCLC中TIL的多维框架，以克服耐药性并优化免疫治疗组合。这些见解共同推动NSCLC免疫治疗朝着精准调节肿瘤免疫微环境的方向发展。
