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