CD274 and melanoma: These studies demonstrate that IFN-γ (1) regulates the expression of targets for ICIs via the canonical JAK/STAT-dependent pathway and (2) triggers negative feedback signaling, which can prevent the development of resistance to ICIs, as elevated expression of PD-L1 on the melanoma cell membrane, for example, can be associated with a worse immune response in patients treated with ICIs [66], as discussed later.