Two recent analyses of various cancers demonstrated that high TMB was associated with ICI benefit in cancers related to environmental carcinogens, such as lung cancer, melanoma, bladder cancer.1,9 Another high TMB subset associated with ICI response was pan-cancers with either mismatch repair deficiency or polymerase deficiency from pathogenic mutation of POLE or POLD1. This evidence concerns the gene POLD1 and cancer.