However, in an already established tumor, the maturation of myeloid cells to macrophages is blocked by multiple factors and mechanisms, such as tumor-derived growth factors (STAT3, IRF8, C/EBPβ, Notch, adenosine receptors A2B signaling, NLRP3), hypoxia, and negative feedback loops (1, 80). The gene discussed is IRF8; the disease is neoplasm.