POLE and cancer: It is becoming increasingly clear that cancers with a high intrinsic mutation load (MMR- and POLE-mutated cancers) or cancers related to mutagenic environmental genotoxic exposure such as lung, melanoma, and bladder cancers, which show all a high mutation burden, respond generally well to immunotherapy (Rizvi et al, 2015; McGranahan et al, 2016; Yarchoan et al, 2017).