Second, a pivotal role of IFNAR1 and IFNGR1 expression (either on immune cells or tumor cells) in governing IOs has been established, but prolonged/sustained IFN signaling could mediate resistance to IOs, either through negative feedback mechanisms such as upregulation of PD-L1, CD47, and YAP, or through epigenetic modifications in the tumor cells. The gene discussed is CD47; the disease is neoplasm.