In murine melanoma models, silencing the IFNGR1 gene nullified the efficacy of anti-CTLA-4.105 IFN-γ has been validated as a promoter of T cell infiltration, upregulating major histocompatibility complex class (MHC) and PD-L1 expression in tumors while limiting the accumulation of immunosuppressive components, such as CXCR2+CD68+ macrophages, in the TME.106,107 Consequently, it is rational to combine IFN-γ with anti-PD-1/PD-L1 for optimal cancer immunotherapy. The gene discussed is IFNG; the disease is cancer.