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Open AccessArticle

High Level Expression of MHC-II in HPV+ Head and Neck Cancers Suggests that Tumor Epithelial Cells Serve an Important Role as Accessory Antigen Presenting Cells

1
Department of Microbiology and Immunology, The University of Western Ontario, London, ON N6A 3K7, Canada
2
Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON N6A 3K7, Canada
3
Department of Oncology, The University of Western Ontario, London, ON N6A 3K7, Canada
4
London Regional Cancer Program, Lawson Health Research Institute, London, ON N6C 2R5, Canada
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1129; https://doi.org/10.3390/cancers11081129
Received: 23 July 2019 / Revised: 3 August 2019 / Accepted: 5 August 2019 / Published: 7 August 2019
(This article belongs to the Special Issue Human Papillomavirus and Cancers)
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Abstract

High-risk human papillomaviruses (HPVs) are responsible for a subset of head and neck squamous cell carcinomas (HNSCC). Expression of class II major histocompatibility complex (MHC-II) is associated with antigen presenting cells (APCs). During inflammation, epithelial cells can be induced to express MHC-II and function as accessory APCs. Utilizing RNA-seq data from over 500 HNSCC patients from The Cancer Genome Atlas, we determined the impact of HPV-status on the expression of MHC-II genes and related genes involved in their regulation, antigen presentation, and T-cell co-stimulation. Expression of virtually all MHC-II genes was significantly upregulated in HPV+ carcinomas compared to HPV− or normal control tissue. Similarly, genes that encode products involved in antigen presentation were also significantly upregulated in the HPV+ cohort. In addition, the expression of CIITA and RFX5—regulators of MHC-II—were significantly upregulated in HPV+ tumors. This coordinated upregulation of MHC-II genes was correlated with higher intratumoral levels of interferon-gamma in HPV+ carcinomas. Furthermore, genes that encode various co-stimulatory molecules involved in T-cell activation and survival were also significantly upregulated in HPV+ tumors. Collectively, these results suggest a previously unappreciated role for epithelial cells in antigen presentation that functionally contributes to the highly immunogenic tumor microenvironment observed in HPV+ HNSCC. View Full-Text
Keywords: human papillomavirus; MHC-II; major histocompatibility complex; antigen presentation; head and neck carcinoma; co-stimulatory molecules; survival signals; T-cell human papillomavirus; MHC-II; major histocompatibility complex; antigen presentation; head and neck carcinoma; co-stimulatory molecules; survival signals; T-cell
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Gameiro, S.F.; Ghasemi, F.; Barrett, J.W.; Nichols, A.C.; Mymryk, J.S. High Level Expression of MHC-II in HPV+ Head and Neck Cancers Suggests that Tumor Epithelial Cells Serve an Important Role as Accessory Antigen Presenting Cells. Cancers 2019, 11, 1129.

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