Targeting Tumor-Associated Macrophages in Cancer Immunotherapy

SIMPLE SUMMARY: Tumor-associated macrophages (TAMs) coinhabit the tumor microenvironment with cancer, immune, and stromal cells. They undermine the immune system and facilitate tumor growth and metastasis. In this review, we discussed current understanding of TAMs functions, and strategies harnessing the knowledge gained from recent research to develop innovative cancer treatments. We summarized pre-clinical/clinical studies targeting TAMs with small molecule inhibitors or antibodies alone or combined with chemotherapy/immunotherapy, evaluated the efficacy of these therapies, and discussed mechanisms of actions. ABSTRACT: Tumor-associated macrophages (TAMs) represent the most abundant leukocyte population in most solid tumors and are greatly influenced by the tumor microenvironment. More importantly, these macrophages can promote tumor growth and metastasis through interactions with other cell populations within the tumor milieu and have been associated with poor outcomes in multiple tumors. In this review, we examine how the tumor microenvironment facilitates the polarization of TAMs. Additionally, we evaluate the mechanisms by which TAMs promote tumor angiogenesis, induce tumor invasion and metastasis, enhance chemotherapeutic resistance, and foster immune evasion. Lastly, we focus on therapeutic strategies that target TAMs in the treatments of cancer, including reducing monocyte recruitment, depleting or reprogramming TAMs, and targeting inhibitory molecules to increase TAM-mediated phagocytosis.