IFNG and hepatocellular carcinoma: The type II interferon, IFN-γ, can be generated by activated T cells and NK (nature killer) cells, and is among the inflammatory cytokines most effective in promoting PD-L1 expression.39 The IFN-γ cell surface receptor comprises 2 subunits, IFNGR1 and IFNGR2, and IFN-γ binding couples the receptor with JAK1 and JAK2, which initiates phosphorylation of downstream STATs.40,41 IRF-1 is among the most important transcription factors in the IFN-γ signaling pathway, and activates PD-L1 by recognizing and binding to IRF-1 response elements (IRE1 and IRE2) in the PD-L1 gene promoter in HCC cells.42