On the one hand, there is evidence that the large amount of lactate in the TME significantly affects the polarization phenotype of macrophages, and that tumor cell-derived lactate induces polarization toward the M2 phenotype by stabilizing HIF-1α and promoting angiogenesis-induced production of VEGF, which phenotype demonstrates greater survival and adaptive capacity than M1 phenotype in the acidic environment of tumor tissues [158, 159]. This evidence concerns the gene HIF1A and neoplasm.