biostudies-literatureValero CNIDCR NIH HHSJayme and Peter Flowers FundGeoffrey Beene Cancer Research CenterNIH/NCISebastian Nativo FundNCI NIH HHSFundación Alfonso Martín EscuderoUS Department of DefenseMSK Population Science Research ProgramNIHe169823https://www.ebi.ac.uk/biostudies/studies/S-EPMC10541199biostudies-literatureUnknown133(19)BACKGROUNDRecurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is generally an incurable disease, with patients experiencing median survival of under 10 months and significant morbidity. While immune checkpoint blockade (ICB) drugs are effective in approximately 20% of patients, the remaining experience limited clinical benefit and are exposed to potential adverse effects and financial costs. Clinically approved biomarkers, such as tumor mutational burden (TMB), have a modest predictive value in HNSCC.METHODSWe analyzed clinical and genomic features, generated using whole-exome sequencing, in 133 ICB-treated patients with R/M HNSCC, of whom 69 had virus-associated and 64 had non-virus-associated tumors.RESULTSHierarchical clustering of genomic data revealed 6 molThe Journal of clinical investigationClinical-genomic determinants of immune checkpoint blockade response in head and neck squamous cell carcinoma.PMC10541199R01 DE027738U54 CA274513Cancer Center Support Grant P30 CA008748R35 CA232097P30 CA008748-CA210784Kaplan SLiu LLee MHan CYMorris LGKoh ESZuur CLHo ALGolkaram MSarkar RPawlowski TFitzgerald CValero CChowell DXu BBoe LAVos JLChan TAPei XPandey ARiaz NSolit DBfalseClinical-genomic determinants of immune checkpoint blockade response in head and neck squamous cell carcinoma.BACKGROUNDRecurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) is generally an incurable disease, with patients experiencing median survival of under 10 months and significant morbidity. While immune checkpoint blockade (ICB) drugs are effective in approximately 20% of patients, the remaining experience limited clinical benefit and are exposed to potential adverse effects and financial costs. Clinically approved biomarkers, such as tumor mutational burden (TMB), have a modest predictive value in HNSCC.METHODSWe analyzed clinical and genomic features, generated using whole-exome sequencing, in 133 ICB-treated patients with R/M HNSCC, of whom 69 had virus-associated and 64 had non-virus-associated tumors.RESULTSHierarchical clustering of genomic data revealed 6 mol2023-01-01T00:00:00Z2023 Oct2026-05-28T22:35:44.609Z2025-02-18T23:59:21.539ZS-EPMC105411993756158310.1172/JCI169823