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Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC

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Item Type:Article
Title:Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC
Creators Name:Messerschmidt, C. and Obermayer, B. and Klinghammer, K. and Ochsenreither, S. and Treue, D. and Stenzinger, A. and Glimm, H. and Fröhling, S. and Kindler, T. and Brandts, C.H. and Schulze-Osthoff, K. and Weichert, W. and Tinhofer, I. and Klauschen, F. and Keilholz, U. and Beule, D. and Rieke, D.T.
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 re-analyzed. 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.
Keywords:Immune Checkpoint Inhibition, Head and Neck Cancer, APOBEC, Mutational Signature, Tumor Inflammation
Source:International Journal of Cancer
Page Range:2293-2302
Date:15 October 2020
Official Publication:https://doi.org/10.1002/ijc.33123
PubMed:View item in PubMed
Related to:
https://edoc.mdc-berlin.de/18167/Preprint version

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