【摘要】 肺癌是全球发病率和死亡率均居首位的恶性肿瘤。近年来免疫检查点抑制剂显著改善了部分晚期非小细胞肺癌患者的生存预后，但仍有相当比例患者存在原发性或继发性免疫耐药。肿瘤微环境（tumor microenvironment, TME）结构重塑被认为是影响免疫治疗疗效的重要因素。胞葬是肿瘤相关巨噬细胞（tumor-associated macrophages, TAMs）清除凋亡细胞的重要过程，在维持炎症消退和组织稳态的同时，可诱导巨噬细胞发生显著的代谢重编程及分泌谱改变。持续活化的胞葬作用通过调控脂质代谢和糖酵解等代谢途径，促进多种免疫抑制及组织修复因子的分泌，从而驱动异常血管生成、激活肿瘤相关成纤维细胞并促进细胞外基质沉积，导致肿瘤基质结构重塑，形成免疫排斥型TME，限制效应T细胞浸润并降低免疫治疗疗效。本文综述胞葬作用在TME中的分子机制，重点阐述其在代谢重编程、血管生成异常及基质纤维化中的作用，并探讨靶向胞葬相关信号通路及TME结构重塑的潜在治疗策略，并进一步探讨胞葬相关指标在免疫检查点抑制剂疗效预测的潜在价值，以期为肺癌免疫治疗耐药的精准干预提供新的研究思路。更多还原

【Abstract】 Lung cancer is one of the most prevalent and lethal malignant tumors worldwide. In recent years, immune checkpoint inhibitors have significantly improved the survival outcomes of some patients with advanced non-small cell lung cancer; however, primary and acquired resistance remain important barriers limiting their clinical efficacy. Research has revealed that structural remodeling of the tumor microenvironment(TME) is one of the key factors involved in immunotherapy resistance. Efferocytosis is an important process by which tumor-associated macrophages clear apoptotic cells. In the lung cancer TME, the high apoptotic cell burden can lead to persistent activation of efferocytosis. Studies have shown that sustained efferocytosis is not merely a process of cellular debris clearance, but can also induce metabolic reprogramming in macrophages, including dysregulated lipid metabolism and enhanced glycolysis, and promote the secretion of immunosuppressive and tissuerepair-related factors.These changes further promote pathological angiogenesis, activation of cancer-associated fibroblasts, and excessive extracellular matrix deposition, thereby driving structural remodeling of the TME and forming an immune-excluded microenvironment characterized by vascular abnormalities and stromal fibrosis.This process restricts effector T-cell infiltration and impairs the efficacy of immune checkpoint inhibitors.This review describes the molecular mechanisms of macrophage efferocytosis in the lung cancer TME, focusing on its regulatory roles in metabolic reprogramming, pathological angiogenesis, and stromal fibrosis, and discusses potential therapeutic strategies targeting efferocytosis-related signaling pathways and TME structural remodeling, aiming to provide new insights into overcoming immunotherapy resistance in lung cancer.更多还原