Tumor-Associated Macrophages in Esophageal Squamous Cell Carcinoma: Underlying Mechanisms and Targeted Therapy Perspectives

Tumor-associated macrophages (TAMs) are a key immune population that influences the immunosuppressive microenvironment and drives the malignant progression of esophageal squamous cell carcinoma (ESCC). This review summarizes the mechanisms by which TAMs promote ESCC progression through facilitating tumor proliferation, angiogenesis, metastasis, and therapeutic resistance. TAM-directed therapeutic strategies have progressed from early methods of depletion and reprogramming to emerging directions such as phenotypic remodeling, phagocytic checkpoint intervention, and precursor cell targeting. However, the compensatory nature and plasticity of the tumor microenvironment limit the efficacy of monotherapy. The combination of TAM-targeted therapies with immune checkpoint inhibitors, chemotherapy, or anti-angiogenic agents shows potential for reversing immunosuppression and overcoming clinical resistance. Future efforts should focus on elucidating TAM heterogeneity using single-cell and spatial multi-omics technologies and advancing the clinical use of biomarkers and smart drug delivery systems, thereby providing novel pathways for optimizing therapeutic strategies for ESCC.