Fig. 3

The regulation of metabolites produced by tumor cells in immune cells

The metabolites are known regulators of immune cell function, such as lactate, fatty acid, PGE₂ and arginine, etc. As a consequence, the accumulation of extracellular lactate and the amino acids arginine, tryptophan, and glutamine in the tumor environment could affect the proliferation, function and differentiation of immune cells, and the production of cytokines. The glucose-deprived, lactic acid-enriched TME impairs T cell and NK cell function and thus antitumor immune responses and polarizes tumor-associated macrophages (TAMs) towards a generally pro-tumor, M2-like phenotype. Competition for amino acids, including arginine and tryptophan, between immune cells and tumor cells can also suppress antitumor immunity. The availability and usage of fatty acids in immune cells within the TME are also influenced by competition with tumor cells. Notably, a high rate of cholesterol esterification in the tumor can impair immune responses and, therefore, disruption of cholesterol esterification in order to increase the concentration of cholesterol in the plasma membranes of immune cells might increase their proliferation and improve their effector function. The generation of prostaglandin E2 (PGE₂), by tumor cells and other immunomodulatory cells is also implicated in the suppression of antitumor responses