Deep mutagenesis of JAK1 and missense mutations altering the INF-γ pathway have been highlighted in colorectal cancer patients refractory to ICB.125 Loss of Polybromo-1 (PBRM1) in renal cell carcinoma (RCC) reduces the interaction between Brahma-related gene 1 (BRG1) with IFNγ2, leading to decreased STAT1 phosphorylation and IFN-γ target genes.126 Knockdown of IFN-γ receptor 1 (IFNGR1) will lead to primary resistance to anti-CTLA-4 therapy in the mouse model. Here, PBRM1 is linked to hereditary clear cell renal cell carcinoma.