肿瘤相关巨噬细胞(tumor-associated macrophages, TAMs)是肺癌及多种实体瘤微环境中高度可塑的先天免疫细胞,参与肿瘤发生、免疫耐药及治疗应答。随着单细胞测序和空间转录组等技术的发展,TAM 的异质性、谱系来源及功能动态逐渐被揭示,挑战了传统M1/M2极化模型。本文综述了TAM 在肺癌中的起源、分布、极化状态及代谢调控,重点阐述了乳酸-低氧轴、脂质与胆固醇代谢对TAM 免疫抑制功能的影响,并梳理其在免疫监视、肿瘤增殖、血管生成、转移及免疫耐药中的作用,特别关注了TREM2+ 脂质相关TAM 亚群在免疫冷区形成与免疫检查点抑制剂耐药中的作用。最后,本文总结了阻断TAM 募集、表型重编程、代谢干预及联合免疫治疗等策略, 并提出基于TAM 异质性的个体化干预设想,为肺癌免疫治疗优化提供理论支持。

Tumor-associated macrophages (TAMs) are highly plastic innate immune cells in the tumor microenvironment of lung cancer and other solid tumors, playing key roles in tumor development, immune resistance, and therapeutic response. With the advent of single-cell sequencing and spatial transcriptomics, the heterogeneity, lineage origins, and dynamic functions of TAMs have been increasingly elucidated, challenging the traditional M1/M2 polarization model. This review summarizes the origins, distribution, polarization states, and metabolic regulation of TAMs in lung cancer, highlighting the impact of lactate-hypoxia axis, lipid metabolism, and cholesterol metabolism on their immunosuppressive functions. We also discuss the roles of TAMs in immune surveillance, tumor proliferation, angiogenesis, metastasis, and immune resistance, with a focus on TREM2+ lipid-associated TAMs in the formation of immune-cold regions and resistance to immune checkpoint inhibitors. Finally, we summarize strategies targeting TAM recruitment, phenotypic reprogramming, metabolic intervention, and combination immunotherapy, and propose personalized interventions based on TAM heterogeneity, providing a theoretical basis for optimizing lung cancer immunotherapy.