A New Perspective in Tumor Therapy: Targeting M2-Type Tumor-Associated Macrophages

Uncontrolled proliferation is not the only factor driving tumor growth; the tumor microenvironment (TME) has a significant impact. Tissue homeostasis and pathogen removal depend on macrophages, which are important innate immune effector cells. Nevertheless, there is growing evidence that tumor-associated macrophages (TAMs) do not consistently suppress cancer and are functionally diverse. Specifically, M2-polarized TAMs (M2-TAMs) build up in multiple solid tumors, where they promote angiogenesis, metastasis, and immunosuppression, hastening the course of the disease. Here, we critically assess the clinical translatability of TAM-targeted treatment approaches, outline the molecular circuits underpinning M2-TAMs–tumor cell interaction, and extensively explore the phenotypic spectrum and functional diversity of macrophages in cancer. Our objective is to offer a theoretical foundation for upcoming immunotherapeutic interventions.