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

Item Type:Preprint
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. Among HPV-negative HNSCC, APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. APOBEC3-enriched HPV-negative HNSCC showed higher T-cell inflammation and immune checkpoint expression. Mutations in immune-evasion pathways were enriched in these tumors. APOBEC3B and 3C expression was identified in tumor cells and correlated with tumor inflammation. 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 Burden, Mutational Signature
Publisher:Cold Spring Harbor Laboratory Press
Article Number:586396
Date:28 March 2019
Official Publication:https://doi.org/10.1101/586396
Related to:
https://edoc.mdc-berlin.de/18995/Final version

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