These proteins are members of a family of non-receptor tyrosine kinases that play a growth-promoting role in tumour cells while concurrently regulating immune responses via several mechanisms.79,80 Loss-of-function mutations in JAK1/2 are associated with acquired resistance to PD-1 blockade in melanoma patients.78 In a mechanistic study, Sucker et al.81 reported mutations in JAK2, which led to increased IFN-γ resistance and subsequent anti-PD-1 therapy failure in melanoma patients. This evidence concerns the gene PDCD1 and melanoma.