Targeting Tumor-Associated Macrophages in Colon Cancer: Mechanisms and Therapeutic Strategies

Jianqin Xiang ^1,2 Jian Wang ² Huihui Xiao ² Chengchen Huang ² Chunrong Wu ² Lin Zhang ³ Chenyuan Qian ^2* Debing Xiang ^1,2*

• ¹ 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China., Luzhou, China
• ² Department of Oncology, Chongqing University Jiangjin Hospital, Chongqing 402260, China., Chongqing, China
• ³ Department of Gastroenterology, Chongqing University Jiangjin Hospital, Chongqing 402260, China., Chongqing, China

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.