The Role of Macrophages in Cancer: From Basic Research to Clinical Applications

Macrophages are innate immune cells that extensively infiltrate and play a key role in the tumor microenvironment (TME). Tumor cell-secreted factors recruit monocytes into the TME, where they differentiate into tumor-associated macrophages (TAMs), which can polarize into distinct phenotypes: M1 and M2. M1 TAMs promote antitumor immunity through cytokine secretion and antigen presentation, whereas M2 TAMs support tumor progression by facilitating angiogenesis, invasion, and immune escape. Despite these dual roles, the specific mechanisms governing macrophage plasticity and polarization remain insufficiently understood. This review comprehensively summarizes the origin, polarization, and functional diversity of macrophages in the TME, with emphasis on pathways that regulate TAM-mediated immune responses. Furthermore, this article examines current TAM-targeted therapeutic strategies, including recruitment inhibition, phenotypic reprogramming, and the development of chimeric antigen receptor macrophages (CAR-Ms), as well as macrophage-based drug delivery and exosome therapy. By integrating recent advances in cell engineering and immunometabolism, this review highlights the translational potential of TAM-targeted therapies and their value in reshaping the immunosuppressive TME to enhance cancer immunotherapy.