Mechanically, the extracellular signal-regulated kinase (ERK)/transcription 3 (STAT3) activation, the activator of STAT3 signaling pathway and stimulated expression of vascular endothelial growth factor (VEGF) and arginase-1 (ARG1), and stabilization of HIF-1a contributes to the lactate-induced M2 macrophages polarization and its pro-tumorigenic effects in breast cancer [58,59]. The gene discussed is VEGFA; the disease is breast cancer.