Figure 2.

Overview of immunosuppressive effects of lactate in the tumor microenvironment (TME). In a hypoxic environment, Glc enters the cell via glucose transporter (GLUT) 1 and is broken down into pyruvate and then in lactate, which is transported out of the cell via monocarboxylated transporter 4 (MCT4). The lactate produced by transformed cells culminates in an acidified TME. This phenomenon is able to suppress the anticancer immune responses, particularly through impaired T and natural killer (NK) cells activation, reduced antigen presentation, compromised dendritic cell (DC) differentiation and maturation. It also promotes the emergence of the M2 Mϕ, which secretes high levels of pro-carcinogenic cytokines, such as transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF), involved in processes such as epithelial–mesenchymal transition (EMT) and angiogenesis, events implicated in metastasis and cancer progression.