Wang F, Zhao Q, Wang YN, et al. - Via a conducted a combined analysis using a large data set (n = 47,721), researchers assessed the POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. Patients with nonmelanoma skin cancer had the greatest levels of POLE/POLD1 mutations. A great frequency of POLE/POLD1 mutations were noted not only in endometrial cancer and colorectal cancer, but also skin cancer, esophagogastric cancer, bladder cancer, lung cancer and others. POLE or POLD1 mutations were a negative prognostic marker and may be used to prognosticate a survival advantage from Immune-checkpoint inhibitor (ICI) therapy across diverse cancer types. Mutations in all exons of these 2 genes should be integrated into predictive biomarker panels for ICI therapy as nonsynonymous mutations in POLE/POLD1 not seen in the exonuclease domain had comparable relations with the OS of patients receiving ICI treatment.