In Reply We thank Drs Cui and Zhang for their comments on our Brief Report.1 We share their interest in studying tumor mutation burden (TMB)—a predictive biomarker associated with the probability that tumors of many different cancer histologies will respond to checkpoint inhibitor immunotherapy. It would be wonderful if the specific numerical value of TMB (in mutations per megabase) that optimally predicted immunotherapy response was the exact same number for every type of cancer and if that numerical value were a convenient number, like 10. Alas, the universe is not so simple.