IFNG and neoplasm: Although tumor cells are still recognized by T cells, their JAK1/2 mutations render them insensitive to the antiproliferative effects of IFN-γ and lack of IFN-γ-induced surface expression of both PD-L1 and MHC class I. Similarly, tumor analysis of patients resistant to treatment with the anti–cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) agent, ipilimumab, revealed that mutations in the IFN-γ pathway genes, IFNGR1/2, JAK1/2, and IRF1, could suppress tumor cells in response to IFN-γ signaling (38).