Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
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Pages (from-to) | 2293-2302 |
Number of pages | 10 |
Journal | International journal of cancer |
Volume | 147 |
Issue number | 8 |
Publication status | Published - 15 Oct 2020 |
Peer-reviewed | Yes |
External IDs
PubMed | 32468570 |
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Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- APOBEC, head and neck cancer, immune checkpoint inhibition, mutational signature, tumor inflammation