Small studies in patients with melanoma, non-small cell lung cancer, and bladder cancer being treated with immune checkpoint inhibitors have demonstrated a positive association between tumors with a high tumor mutational burden, determined by whole exome sequencing, and response to CTLA-4 blockade and PD-1/PD-L1 inhibition independent of PD-L1 status [98,99,100,101]. This evidence concerns the gene CD274 and urinary bladder cancer.