POLE and cancer: These genes should be carefully selected by including the following: (i) other TMB-related marker genes, such as POLE whose mutations are associated with TMB-H in multiple solid tumor types like endometrial, CRC, gastric, melanoma, lung, and pediatric cancers (60–62), or BRAF and MET whose alterations are associated with longer duration of ICI treatment; (ii) other immunotherapy response-related genes, such as genes for MSI estimate, immune resistant gene, IDO1, and JAK (4, 5); (iii) multiple types of alterations, such as mutations, indels, amplifications, CNAs, and structure variations.