Persistent IFN-gamma stimulation renders susceptible melanoma cells resistant to immunotherapy[69]; while the increased frequency of mutations in the IFN-gamma pathway genes (IFN-gamma receptor 1 and 2, JAK2, and interferon regulatory factor 1) were detected through the analysis of tumor cells in patients who did not respond to anti-CTLA-4 therapy[70]. This evidence concerns the gene IFNG and melanoma.