Characteristics of TAMs
TAMs are the most abundant immune cells in the TME with phenotypic heterogeneity and functional diversity, the phenotype and exact role of TAMs are still controversial. What is certain is that M1 killer-like TAMs trigger inflammation and direct T cells towards T helper 1 (Th1) tumoricidal responses; M2 repair-like TAMs promote cancer progression, not only by promoting tumor survival and proliferation, vascular generation and metastasis, but also suppress anti-tumor immune responses[6, 8, 30]. The polarization of M1-like macrophages is characterized by decreased phagocytosis, NF-κB signaling activation and release of pro-inflammatory cytokines including IL-1β, IL-6, CXCL9, TNF-α and CXCL10 to promote inflammation and exacerbate tissue damage[31, 32]. During tumor development, pro-inflammatory effects are exerted through M1 macrophages to inhibit tumor progression[33]. M2 macrophages are essentially characterized by elevated levels of arginase-1 (Arg-1) and using phagocytosis to repair damaged tissues, can lead to the vascularization of solid tumor tissues, thus promoting tumor cell proliferation in cancer angiogenesis with anti-inflammatory effects and promote tumor cell proliferation[34], and can aid in tumor metastasis, promote regeneration by making tumor cells resistant to chemotherapy and promote immunosuppressive signaling in tumors by inhibiting cytotoxic T cells[33, 35, 36]. Notably, TAMs secrete molecules such as Arg1, IL-10 and TGF-β1, forming paracrine and autocrine loops[37]. Arg1+ macrophages are more abundant in tumors, and Arg1 release is influenced by autophagy[38, 39]. IL-10 directly suppresses T cell function, while TGF-β1 exerts immunosuppression, promotes cancer cell proliferation, and induces epithelial to mesenchymal transition and cancer stem cell generation[40, 41]. Interestingly, M1 macrophages exhibit a metabolic profile dominated by aerobic glycolysis, similar to the Warburg effect in tumor cells; in contrast, M2 macrophages use OXPHOS as the main metabolic method[42]. Autophagy was shown to contribute to macrophage polarization toward the pro-inflammatory and more glycolytic M1 phenotype, but not the OXPHOS phenotypic M2 polarization[43]. However, exceptions have been observed, where the major subtype of the TAMs might be the anti-tumor M1 macrophages instead of M2. Meanwhile, M1 macrophages might contribute to tumor malignancy as well[44]. Therefore, clarifying the phenotype and function of TAMs and elucidating the specific differences between M1 and M2 types are crucial for tumor research and treatment (Table 1).
Table 1. The basic characteristics between M1 and M2