6533b85bfe1ef96bd12bb575
RESEARCH PRODUCT
Distinct immune evasion in APOBEC ‐enriched, HPV ‐negative HNSCC
Denise TreueClemens MesserschmidtDamian T. RiekeDieter BeuleDieter BeuleBenedikt ObermayerStefan FröhlingKlaus Schulze-osthoffKlaus Schulze-osthoffIngeborg TinhoferIngeborg TinhoferU. KeilholzU. KeilholzChristian BrandtsChristian BrandtsAlbrecht StenzingerAlbrecht StenzingerThomas KindlerThomas KindlerFrederick KlauschenFrederick KlauschenWilko WeichertWilko WeichertSebastian OchsenreitherSebastian OchsenreitherHanno GlimmHanno GlimmKonrad Klinghammersubject
MaleAPOBECCancer ResearchT-Lymphocytesmedicine.medical_treatment610BiologyCohort Studies03 medical and health sciences0302 clinical medicineGene expressionBiomarkers TumormedicineHumansExomeAPOBEC Deaminasestumor inflammationPapillomaviridaeExomeGeneImmune EvasionInflammationSequence Analysis RNASquamous Cell Carcinoma of Head and NeckPapillomavirus InfectionsAPOBECmutational signatureImmunotherapyMiddle Agedmedicine.diseaseHead and neck squamous-cell carcinomaPhenotypeImmune checkpointddc:Gene Expression Regulation Neoplasticstomatognathic diseasesOncologyHead and Neck Neoplasms030220 oncology & carcinogenesisMutationCancer researchimmune checkpoint inhibitionFemalehead and neck cancerTranscriptome600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheitdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-01-01 | International Journal of Cancer |