IFNG and melanoma: In a separate study, Zaretsky et al. reported loss-of-function mutations of JAK1 and JAK2 in two out of four melanoma patients that developed therapeutic resistance to anti-PD-1; both JAK1/2 mutations were coupled with a total loss of functional response to IFN-γ and JAK1 mutation also caused loss of functional response to IFN-α/β [94].