Tumor-Associated Macrophage Subsets: Shaping Polarization and Targeting

The tumor microenvironment (TME) is a critical regulator of tumor growth, progression, and metastasis. Among the innate immune cells recruited to the tumor site, macrophages are the most abundant cell population and are present at all stages of tumor progression. They undergo M1/M2 polarization in response to signals derived from TME. M1 macrophages suppress tumor growth, while their M2 counterparts exert pro-tumoral effects by promoting tumor growth, angiogenesis, metastasis, and resistance to current therapies. Several subsets of the M2 phenotype have been observed, often denoted as M2a, M2b, M2c, and M2d. These are induced by different stimuli and differ in phenotypes as well as functions. In this review, we discuss the key features of each M2 subset, their implications in cancers, and highlight the strategies that are being developed to harness TAMs for cancer treatment.