IFNG and melanoma: Another study has demonstrated that human melanoma cell lines harboring loss-of-function mutations of JAK2 failed to upregulate PD-L1 in response to IFN-γ exposure (71), implying that patients with defective JAK2-harboring tumors would result in the absence of inducible PD-L1 expression and be unlikely to benefit from anti-PD-1 therapy, representing primary resistance.