From dichotomy to diversity: deciphering the multifaceted roles of tumor-associated macrophages in cancer progression and therapy

Abstract

Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body. Macrophages orchestrate sophisticated processes in development, homeostasis, immunity, and disease1. Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages (TAMs) and promote or inhibit tumor growth depending on the activation state2. TAMs often predominantly display pro-tumorigenic properties that promote inflammation, angiogenesis, metastasis, and immunosuppression. Nevertheless, TAMs also have the potential to serve as anti-tumor effectors and boost anti-tumor immunity. Thus, targeting TAMs is a promising therapeutic strategy3. Antibody-mediated depletion of TAMs has shown promise in preclinical models. Numerous clinical trials are now evaluating macrophage-targeting strategies, often in combination with other immunotherapies4. Furthermore, harnessing the anti-tumor functions of macrophages, especially by enhancing M1 polarization and concurrently inhibiting M2 polarization, also represents a promising therapeutic strategy5.