Conversely, JAK1/2 and APLNR loss-of-function mutations, which result in non-inducibility of tumor PD-L1 expression by IFN-γ, have been associated with primary or acquired resistance to PD-1 blockade in solid tumors; PD-1 blockade was ineffective for these patients even if their mutational load was high (239–241). The gene discussed is IFNG; the disease is neoplasm.