Tumor-Associated Macrophages as Major Immunosuppressive Cells in the Tumor Microenvironment

Simple Summary The tumor microenvironment (TME) refers to the area immediately surrounding a cancerous tumor that influences the tumor's behavior and how the immune system reacts to it. Central to the TME environment are special immune cells-tumor-associated macrophages (TAMs)-that, rather than restrict the tumor, actually facilitate tumor growth and metastasis. Thus, targeting these TAMs can help to eliminate cancer. In this article, we review the biology of TAMs and delve into the signaling mechanisms underlying the polarization of macrophage phenotypes, their plasticity, and therapeutic implications.Abstract Within the tumor microenvironment, myeloid cells constitute a dynamic immune population characterized by a heterogeneous phenotype and diverse functional activities. In this review, we consider recent literature shedding light on the increasingly complex biology of M2-like immunosuppressive tumor-associated macrophages (TAMs), including their contribution to tumor cell invasion and metastasis, stromal remodeling (fibrosis and matrix degradation), and immune suppressive functions, in the tumor microenvironment (TME). This review also delves into the intricate signaling mechanisms underlying the polarization of diverse macrophage phenotypes, and their plasticity. We also review the development of promising therapeutic approaches to target these populations in cancers. The expanding knowledge of distinct subsets of immunosuppressive TAMs, and their contributions to tumorigenesis and metastasis, has sparked significant interest among researchers regarding the therapeutic potential of TAM depletion or phenotypic modulation.