Mechanistically, the activation of extracellular signal-regulated kinase (ERK)/transcription 3 (STAT3), the activator of the STAT3 signaling pathway and the stimulated expression of vascular endothelial growth factor (VEGF) and arginase-1 (ARG1), as well as the stabilization of the hypoxic inducible factor 1 (HIF-1) contribute to lactate-induced polarization of M2 macrophages and its protumorigenic effects in breast cancer [59, 60]. The gene discussed is STAT3; the disease is breast cancer.