Lactate promotes vascular endothelial growth factor (VEGF) secretion by activating the mTORC1 signaling pathway and inhibiting ATP6V0d2-mediated degradation of HIF-2α lysosomes (121); lactate activates the mTORC2-AKT and ERK signaling pathways in tumor-associated macrophages (TAMs) leading to the up-regulation of PD-L1 expression (122); and lactate induces the expression of HF2α in tumor-associated macrophages (TAMs) through MCT1 endocytosis. The gene discussed is EPAS1; the disease is neoplasm.