Xiang Jianqin, Wang Jian, Xiao Huihui, Huang Chengchen, Wu Chunrong, Zhang Lin, Qian Chenyuan, Xiang Debing
Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Department of Oncology, Chongqing University Jiangjin Hospital, Chongqing, China.
Front Immunol. 2025 Mar 21;16:1573917. doi: 10.3389/fimmu.2025.1573917. eCollection 2025.
Colon cancer (CC) remains a primary contributor to cancer-related fatalities worldwide, driven by difficulties in early diagnosis and constrained therapeutic options. Recent studies underscore the importance of the tumor microenvironment (TME), notably tumor-associated macrophages (TAMs), in fostering malignancy progression and therapy resistance. Through their inherent plasticity, TAMs facilitate immunosuppression, angiogenic processes, metastatic spread, and drug tolerance. In contrast to M1 macrophages, which promote inflammatory and tumoricidal responses, M2 macrophages support tumor expansion and dissemination by exerting immunosuppressive and pro-angiogenic influences. Consequently, manipulating TAMs has emerged as a potential avenue to enhance treatment effectiveness. This review outlines the origins, polarization states, and functions of TAMs in CC, highlights their role in driving tumor advancement, and surveys ongoing efforts to target these cells for better patient outcomes. Emerging therapeutic strategies aimed at modulating TAM functions - including depletion strategies, reprogramming approaches that shift M2-polarized TAMs toward an M1 phenotype, and inhibition of key signaling pathways sustaining TAM-mediated immunosuppression-are currently under active investigation. These approaches hold promise in overcoming TAM - induced resistance and improving immunotherapeutic efficacy in CC.
结肠癌（CC）仍然是全球癌症相关死亡的主要原因，这是由早期诊断困难和治疗选择有限所致。最近的研究强调了肿瘤微环境（TME），尤其是肿瘤相关巨噬细胞（TAM），在促进恶性肿瘤进展和治疗抵抗中的重要性。通过其固有的可塑性，TAM促进免疫抑制、血管生成过程、转移扩散和药物耐受性。与促进炎症和杀肿瘤反应的M1巨噬细胞相反，M2巨噬细胞通过发挥免疫抑制和促血管生成作用来支持肿瘤的扩展和播散。因此，操控TAM已成为提高治疗效果的一个潜在途径。本综述概述了CC中TAM的起源、极化状态和功能，强调了它们在推动肿瘤进展中的作用，并审视了为改善患者预后而针对这些细胞的正在进行的研究工作。旨在调节TAM功能的新兴治疗策略——包括清除策略、将M2极化的TAM重编程为M1表型的方法，以及抑制维持TAM介导的免疫抑制的关键信号通路——目前正在积极研究中。这些方法有望克服TAM诱导的耐药性并提高CC的免疫治疗疗效。
