Fig. 3

Metabolic regulation of immune cells in cancer. During the development and progression of cancer, dramatic metabolic reprogramming happens in tumor cells and immune cells. Tumor cells have high metabolic demand and metabolic competition with immune cells. The tumor microenvironment is an immunosuppressive environment with the proportion of proinflammatory immune cells decreasing and anti-inflammatory cells increasing. Tumor derived-lactate is an important metabolite to regulate the phenotypes of immune cells. M2 macrophages have an abnormally high capacity to take up glucose, while glucose metabolism is reduced in effector T cells and glycolysis. Nuclear factor-kappaB (NF-κB), Toll-like receptor-2 (TLR2) and forkhead/winged helix transcriptional factor P3 (FoxP3) can regulate glucose metabolism. Lipid accumulation is upregulated in M2 macrophages and effector T cells, and lipid synthesis is upregulated in regulatory T (Treg) cells mediated by sterol regulatory-element binding proteins (SREBPs). Fatty acid oxidation (FAO) is active in M2 macrophages, with peroxisome proliferator-activated receptor γ (PPARγ) and CD36 involved in the regulation. Glutamine metabolism and serine synthesis is increased in M2 macrophages, and protein kinase RNA-like ER kinase can upregulate the serine synthesis. In effector T cells, glutamine uptake is reduced