We previously demonstrated that low TMB of <5 mutations/Mb and high TMB of ⩾20 mutations/Mb portends better prognosis in ICI naïve patients while intermediate TMB, defined as >5 mutations/Mb and <20 mutations/Mb, correlates with worse prognosis.11 Studies demonstrate that the immune signature in cancers with low and high TMB can differ depending on the type of cancer, which could explain some inconsistencies in the association between TMB and ICI outcomes.12 Furthermore, increased PD-L1 expression is correlated with worse prognosis in multiple solid cancer types.13 This evidence concerns the gene CD274 and cancer.