STAT1 and melanoma: The Immunosuppressive Effects of the IFN–JAK–STAT axis (The Yin): In contrast to the positive roles of IFNAR1 expression and IFN-γ signaling in governing IOs, a recent study reported that prolonged IFN-γ (but not IFN-Is) exposure rendered B16-F10 melanoma cells resistant to ICBs+RT via STAT1-mediated epigenomic changes.