Mechanistically, tumors with high lactate output and MCT4-dependent efflux polarize macrophages toward suppressive states and limit CD8+ infiltration (38); converging evidence across cancers indicates that therapeutic interference with lactate production/transport (e.g., LDH/MCT inhibition) can convert non-inflamed microenvironments to T-cell–permissive states (39) (Figure 2). The gene discussed is CD8A; the disease is cancer.