Fig. 2
From: Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors
The role of IFN-γ signaling pathway in adaptive immune resistance and immune surveillance. IFN-γ binds to IFN-γ receptor (IFNGR) on the tumor cell membrane and then activates associated Janus kinase (JAK). Subsequent recruitment and phosphorylation of signal transducers and activators of transcription 1 (STAT1) regulate transcription of Interferon Regulatory Factor-1(IRF-1) in nucleus. IRF-1 promotes PD-L1 expression while interferon-stimulated gene (ISG) transcription induced by phosphorylated STAT1 enhances immune response and inhibits tumor proliferation. Phosphoinositide 3-kinase (PI3K)-AKT pathway promotes activation of STAT1. Constant exposure to IFN-γ by anti-PD-1/PD-L1 results in survival selective pressure. Accumulated IFN-γ signaling pathway mutation or epigenetic alteration abrogates CD8+ T cell mediated tumor cytotoxicity