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

Steven F Gameiro; Farhad Ghasemi; John W Barrett; Anthony C Nichols; Joe S Mymryk

doi:10.3390/cancers11081129

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 (Basel). 2019 Aug 7;11(8):1129. doi: 10.3390/cancers11081129.

Authors

Steven F Gameiro¹, Farhad Ghasemi², John W Barrett², Anthony C Nichols^{2

3

4}, Joe S Mymryk^{5

6

7

8}

Affiliations

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.
⁵ Department of Microbiology and Immunology, The University of Western Ontario, London, ON N6A 3K7, Canada. jmymryk@uwo.ca.
⁶ Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON N6A 3K7, Canada. jmymryk@uwo.ca.
⁷ Department of Oncology, The University of Western Ontario, London, ON N6A 3K7, Canada. jmymryk@uwo.ca.
⁸ London Regional Cancer Program, Lawson Health Research Institute, London, ON N6C 2R5, Canada. jmymryk@uwo.ca.

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.

Keywords: MHC-II; T-cell; antigen presentation; co-stimulatory molecules; head and neck carcinoma; human papillomavirus; major histocompatibility complex; survival signals.

Abstract

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