Metabolic reprogramming is a hallmark of solid cancers. Macrophages as major constituents of immune system take important roles in regulation of tumorigenesis. Pro-tumor M2 macrophages preferentially use oxidative phosphorylation (OXPHOS) to meet their metabolic demands, while anti-tumor M1 macrophages use glycolysis as their dominant metabolic source. Dysregulation in metabolic systems is a driving force of skewing macrophages from M1 toward M2 phenotypical state. Hyperactive M1 macrophages, for instance, release metabolic products that are contributed to M2 macrophage polarization. Thus, metabolic remodeling through reinstating normalization in metabolic systems can be an effective tool in cancer therapy. The key focus of this review is over metabolic systems in macrophages and factors influencing their metabolic acquisition and reprogramming in cancer, as well as discussing bout strategies to adjust macrophage metabolism and reeducation toward M1-like phenotype.
Keywords: Tumor microenvironment (TME); glycolysis; hypoxia; hypoxia inducible factor (HIF); lactate; macrophage; metabolism; oxidative phosphorylation (OXPHOS).
M1 and M2 macrophages evolve diverse metabolic priorities.Strike for utilizing TME metabolic sources hampers M1 macrophage polarization.Hyperactive M1 macrophages skew TME macrophages toward M2 phenotype.Shifting TAM metabolism more into glycolysis is important therapeutically.Transient HIF-1low condition favors M1 phenotypical acquisition, whereas consistent HIF-1/lactate high favors M2 polarization.