1. Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC.
- Author
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Messerschmidt C, Obermayer B, Klinghammer K, Ochsenreither S, Treue D, Stenzinger A, Glimm H, Fröhling S, Kindler T, Brandts CH, Schulze-Osthoff K, Weichert W, Tinhofer I, Klauschen F, Keilholz U, Beule D, and Rieke DT
- Subjects
- Biomarkers, Tumor genetics, Biomarkers, Tumor immunology, Cohort Studies, Exome genetics, Exome immunology, Female, Gene Expression Regulation, Neoplastic genetics, Gene Expression Regulation, Neoplastic immunology, Head and Neck Neoplasms virology, Humans, Inflammation genetics, Inflammation immunology, Inflammation virology, Male, Middle Aged, Mutation genetics, Papillomaviridae immunology, Papillomavirus Infections genetics, Papillomavirus Infections immunology, Papillomavirus Infections virology, Sequence Analysis, RNA methods, Squamous Cell Carcinoma of Head and Neck virology, T-Lymphocytes immunology, Transcriptome genetics, Transcriptome immunology, APOBEC Deaminases genetics, APOBEC Deaminases immunology, Head and Neck Neoplasms immunology, Immune Evasion genetics, Immune Evasion immunology, Squamous Cell Carcinoma of Head and Neck genetics, Squamous Cell Carcinoma of Head and Neck immunology
- Abstract
Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (n = 496) and a validation set (DKTK MASTER cohort, n = 10). Public single-cell gene expression data from 17 HPV-negative HNSCC were separately reanalyzed. APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. This association was restricted to HPV-negative HNSCC samples. An APOBEC-enriched, HPV-negative subgroup was identified, that showed higher T-cell inflammation and immune checkpoint expression, as well as expression of APOBEC3 genes. Mutations in immune-evasion pathways were also enriched in these tumors. Analysis of single-cell sequencing data identified expression of APOBEC3B and 3C genes in malignant cells. We identified an APOBEC-enriched subgroup of HPV-negative HNSCC with a distinct immunogenic phenotype, potentially mediating response to immunotherapy., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Published
- 2020
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