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. 2020 Feb 27;11:279. doi: 10.3389/fimmu.2020.00279

Figure 2.

Figure 2

Impact of lactic acid on immune cells in the tumor microenvironment. Enhanced secretion of lactic acid by tumors induces a drop in the extracellular pH and acidification of the tumor microenvironment. There are multiple immune cells in the tumor microenvironment, including TAMs, CTLs, DCs, and NK cells. Increased extracellular concentrations of lactic acid play an important role in tumor escape of immune surveillance. (a), Within activated T cells, a high concentration of extracellular lactic acid from the tumors inhibits the release of lactic acid from T cells. The accumulation of intracellular lactic acid in T cells inhibits glycolysis metabolism and blocks the production of cytokines (particularly IFN-γ, TNF-α, and IL-2). (b), Within macrophages, lactic acid promotes the M2-like polarization of TAMs, generates anti-inflammatory cytokines, such as IL-10 and TGF-β, and increases the production of VEGF and Arg1 for tumor angiogenesis. (c), Within dendritic cells, lactic acid is responsible for the differentiation of tolerogenic DCs and the generation of IL-10. (d), Within NK cells, lactic acid impairs the cytotoxic activity of NK cells. Abbreviations: MCT, monocarboxylic acid transporter; Glut, glucose transporter; NFAT, nuclear factor of activated T cells; TAM, tumor-associated macrophage; CTL, cytotoxic T lymphocyte; VEGF, vascular endothelial growth factor; and Arg1, arginase 1.