IL-6 and CSF-1 (colony-stimulating factor-1) when present in the necrotic tumor microenvironment may induce synergistic activation of IL-6 and CSF-1 downstream pathways which promote PPARγ (peroxisome proliferator-activated receptor-γ)-dependent HIF-2α (hypoxia-inducible factor-2α) transcription resulting in a robust ARG-1 upregulation in BMDMs [28]. This evidence concerns the gene EPAS1 and neoplasm.