Tumor-associated Macrophage: Polarization, Immunoregulation and Immunotherapy

Multiple immune cells and stromal components comprise the tumor microenvironment (TME). In this complex TME, tumor-associated macrophages (TAMs) are spatially heterogeneous. Tumor heterogeneity affects tissue remodeling, immune response, angiogenesis, and metastatic potential. This review highlights the roles of macrophages in TME, immunoregulation, and immunotherapy. Also, intricate relationships between TAMs and various immune cells in the TME and immune evasion have been explored comprehensively. TAM heterogeneity and complex interactions with immune cell types may lead to potential therapeutic approaches. Similarly, classic immune checkpoint inhibitors like anti-PD-L-1 and anti-PD-1 offer promising tumor therapies. TAMs regulate PD-1/PD-L1 immunosuppression by suppressing T cell recruitment and function using cytokines, superficial immune checkpoint ligands, and exosomes. TAM’s functions and mechanisms in PD-1/PD-L1 blocker resistance are described in detail. The insights into intricate relationships of TAMs with the immune cells within TME and the role of immune checkpoint inhibitors will further help explore potential future therapeutic advances.