HIF1A and neoplasm: The lactic acid present in the TME along with the hypoxic environment is also known to mediate the transformation of the macrophages from M1 to a pro-tumorigenic M2 phenotype through a HIF1α-mediated pathway (115, 116) by directly inducing M2-like gene expression (augmented expression of VEGF, Arg1, PKM2, etc.)in tumor-associated macrophages (TAMs) (116, 117).