RT Journal Article SR Electronic T1 dN/dS dynamics quantify tumour immunogenicity and predict response to immunotherapy JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.21.215038 DO 10.1101/2020.07.21.215038 A1 Luis Zapata A1 Giulio Caravagna A1 Marc J Williams A1 Eszter Lakatos A1 Khalid AbdulJabbar A1 Benjamin Werner A1 Trevor A Graham A1 Andrea Sottoriva YR 2020 UL http://biorxiv.org/content/early/2020/07/22/2020.07.21.215038.abstract AB Immunoediting is a major force during cancer evolution that selects for clones with low immunogenicity (adaptation), or clones with mechanisms of immune evasion (escape). However, quantifying immunogenicity in the cancer genome and how the tumour-immune coevolutionary dynamics impact patient outcomes remain unexplored. Here we show that the ratio of nonsynonymous to synonymous mutations (dN/dS) in the immunopeptidome quantifies tumor immunogenicity and differentiates between adaptation and escape. We analysed 8,543 primary tumors from TCGA and validated immune dN/dS as a measure of selection associated with immune infiltration in immune-adapted tumours. In a cohort of 308 metastatic patients that received immunotherapy, pre-treatment lesions in non-responders showed increased immune selection (dN/dS<1), whereas responders did not and instead harbour a higher proportion of genetic escape mechanisms. Ultimately, these findings highlight the potential of evolutionary genomic measures to predict clinical response to immunotherapy.Competing Interest StatementThe authors have declared no competing interest.