Viruses 2017, 9(9), 252; https://doi.org/10.3390/v9090252
Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection
Steven F. Gameiro 1, Ali Zhang 1, Farhad Ghasemi 2, John W. Barrett 2, Anthony C. Nichols 2,3,4
and Joe S. Mymryk 1,2,3,4,*
and Joe S. Mymryk 1,2,3,4,*
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.
Academic Editor: Eric O. Freed
Received: 12 July 2017 / Revised: 31 August 2017 / Accepted: 2 September 2017 / Published: 10 September 2017
(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)
Abstract
Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 human cervical and head & neck tumors from The Cancer Genome Atlas (TCGA), we determined the impact of HPV status on the mRNA expression of all six MHC-I heavy chain genes, and the β2 microglobulin light chain. Unexpectedly, these genes were all expressed at high levels in HPV positive (HPV+) cancers compared with normal control tissues. Indeed, many of these genes were expressed at significantly enhanced levels in HPV+ tumors. Similarly, the transcript levels of several other components of the MHC-I peptide-loading complex were also high in HPV+ cancers. The coordinated expression of high mRNA levels of the MHC-I antigen presentation apparatus could be a consequence of the higher intratumoral levels of interferon γ in HPV+ carcinomas, which correlate with signatures of increased infiltration by T- and NK-cells. These data, which were obtained from both cervical and oral tumors in large human cohorts, indicates that HPV oncoproteins do not efficiently suppress the transcription of the antigen presentation apparatus in human tumors. View Full-TextKeywords:
human papillomavirus; MHC-I; major histocompatibility complex; antigen presentation; immune evasion; head & neck carcinoma; cervical carcinoma
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Gameiro, S.F.; Zhang, A.; Ghasemi, F.; Barrett, J.W.; Nichols, A.C.; Mymryk, J.S. Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection. Viruses 2017, 9, 252.
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