Fig. 2. Tumor cell glycolysis creates an acidic micro-environment.

Tumor cells, through aerobic glycolysis, produce lactate that will be exported in the tumor micro-environment via MCT1 and MCT4 transporters. Lactate has a direct tolerogenic effect by modulating T cells and NK cells activation as well as tumor-associated dendritic cells differentiation and M2 macrophages polarization. Lactate export also impacts micro-environment pH by inducing acidosis that will participate in the impairment of T cells and NK cells cytotoxicity, M2 polarization, and upregulation of immune checkpoints.