Tumor-Associated Macrophages in Tumor Immunity

Abstract

Tumor-associated macrophages (TAMs) represent one of the main tumor-infiltrating immune cell types and are generally categorized into either of two functionally contrasting subtypes, namely classical activated M1 macrophages and alternatively activated M2 macrophages. The former typically exerts anti-tumor functions, including directly mediate cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; the latter can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis, and lead to tumor progression. Both M1 and M2 macrophages have high degree of plasticity and thus can be converted into each other upon tumor microenvironment changes or therapeutic interventions. As the relationship between TAMs and malignant tumors becoming clearer, TAMs have become a promising target for developing new cancer treatment. In this review, we summarize the origin and types of TAMs, TAMs interaction with tumors and tumor microenvironment, and up-to-date treatment strategies targeting TAMs.

Keywords: immunosuppression; regulation; tumor microenvironment; tumor therapy; tumor-associated macrophages.

Figure 1

A schematic representation of the roles of tumor-associated macrophages (TAMs) in tumor progression. TAMs can mediate immune response, tumor cell proliferation and invasion, angiogenesis and metastasis. MMP, matrix metalloprotein; M-MDSCs, monocyte-related myeloid-derived suppressor cells; CSF1, macrophage colony-stimulating factor; VEGF, vascular endothelial growth factor; ROS, reactive oxygen species; INOS, nitric oxide synthases; LIF, leukocytosis induced factor.

Figure 2

Overview of the factors regulating TAMs functions and the targets of TAMs for cancer treatment. TAMs are a collection of multiple cell types with a wide range of functional effects, which are regulated by many different factors, such as the tumor cell-derived soluble molecules, tumor metabolic alterations, and other immune cells. Targeting TAMs is a new cancer treatment strategy, including limiting monocytes recruitment, targeting TAMs activation, and targeting TAMs specific markers. AHR, aromatic hydrocarbon receptor; SUCNR1, succinate Receptor 1; EGF, epidermal cell growth factor; SIRPα, signal regulatory protein alpha.