Fig. 1.

Schematic diagram of high TMB and low TMB tumors versus hot and cold tumor types and their likelihood of response to ICIs. Tumors with higher somatic mutation prevalence such as melanoma and NSCLC are among high TMB tumors (highly mutated). However, some high TMB tumors can be either hot (T-cell-inflamed) or cold (non-T-cell-inflamed) based on their T-cell and IFN signature (immune phenotype). MMR-deficient CCR cancers are both high TMB and immunologically hot, while MSS CCRs have relatively high mutation rate, but non-T-cell-inflamed. HPV⁺ HNSCC are similar to HPV⁻ HNSCC in their mutation burden, but are more T-cell-inflamed. MCC, ovarian cancer, and RCC have modest mutation rates with a relatively T-cell-inflamed phenotype. Neuroblastoma, prostate, and pancreatic cancers are both immunologically cold and have relatively low mutation burden