Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection

Viruses. 2017 Sep 10;9(9):252. doi: 10.3390/v9090252.

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.

Keywords: MHC-I; antigen presentation; cervical carcinoma; head & human papillomavirus; immune evasion; major histocompatibility complex; neck carcinoma.

MeSH terms

  • Antigen Presentation
  • Female
  • Gene Expression
  • Genes, MHC Class I*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / virology*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / genetics
  • Killer Cells, Natural / immunology
  • Mutation
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / immunology*
  • Papillomavirus Infections / virology
  • T-Lymphocytes / immunology
  • Transcription, Genetic*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / virology*
  • beta 2-Microglobulin / genetics

Substances

  • Histocompatibility Antigens Class I
  • Papillomavirus E7 Proteins
  • beta 2-Microglobulin
  • Interferon-gamma