Since lactate is one of the most abundant metabolites in the TME (64, 94) its presence causes NFAT-regulated NK and CD8+ T cell suppression (21), impairment of NK cell cytolytic function (15, 34, 37) or inhibition of antigen presentation by DCs (49), which impairs the anti-tumor functions of these cell types (21, 45, 49, 95). The gene discussed is CD8A; the disease is neoplasm.