Figure 3.

MAF immunomodulatory functions. MAFs generate an immunosuppressed melanoma microenvironment by multiple mechanisms. They increase the expression of various inflammatory and immunosuppressive factors, including TGF-β, IL-6, MMPs, PGE2, COX-2, CXCL5, and PDL1/2, which dramatically impair the anti-tumor activity of immune cells. Furthermore, MAFs alter the extracellular availability of lactate, glucose, and arginine, which are important immune-modulating metabolites involved in immune cell suppression or polarization toward a tumor-promoting phenotype. Consequently, the generation of an immunosuppressive, glucose- and arginine-poor, lactate-rich melanoma microenvironment allows melanoma cells to evade immune surveillance and thus survive and proliferate safely in the tumor mass.