The metabolic regulation of tumor-associated macrophage reprogramming

Abstract

Tumor-associated macrophages (TAMs) are an essential component of the immune cells that infiltrate the tumor microenvironment (TME) and exhibit immunosuppressive functions. These macrophages exhibit significant phenotypic plasticity and heterogeneity, highlighting their capacity to adapt to various environmental signals. This adaptability facilitates polarization shifts between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. As tumors proliferate and metastasize, the TME progressively transforms into an immunosuppressive environment. Consequently, TAMs undergo metabolic reprogramming in pathways such as glucose, lipid, and amino acid metabolism, among others, which ultimately drive the establishment of an immunosuppressive phenotype. While TAMs do not strictly conform to the M1 and M2 classifications, they often exhibit characteristics resembling M2 macrophages, thereby promoting tumor growth via immunosuppression. This review aims to elucidate the metabolic reprogramming of TAMs and investigate how they maintain their immunosuppressive phenotype, highlighting potential avenues for metabolic therapies.