Current immunotherapies for advanced stage melanomas involve antagonization of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4, ipilimumab) and programmed cell death protein-1 (PD-1, nivolumab and pembrolizumab), but in 45-70% of cases these therapies encounter primary resistance (Table 1) (5, 11). The gene discussed is CTLA4; the disease is melanoma.