Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours

Immunology. 2008 Feb;123(2):218-27. doi: 10.1111/j.1365-2567.2007.02689.x. Epub 2007 Aug 28.


Epigenetic events play an important role in tumour progression and also contribute to escape of the tumour from immune surveillance. In this study, we investigated the up-regulation of major histocompatibility complex (MHC) class I surface expression on tumour cells by epigenetic mechanisms using a murine tumour cell line expressing human E6 and E7 human papilloma virus 16 (HPV16) oncogenes and deficient in MHC class I expression, as a result of impaired antigen-presenting machinery (APM). Treatment of the cells with the histone deacetylase inhibitor Trichostatin A, either alone or in combination with the DNA demethylating agent 5-azacytidine, induced surface re-expression of MHC class I molecules. Consequently, the treated cells became susceptible to lysis by specific cytotoxic T lymphocytes. Further analysis revealed that epigenetic induction of MHC class I surface expression was associated with the up-regulation of APM genes [transporter associated with antigen processing 1 (TAP-1), TAP-2, low-molecular-mass protein 2 (LMP-2) and LMP-7]. The results demonstrate that expression of the genes involved in APM are modulated by epigenetic mechanisms and suggest that agents modifying DNA methylation and/or histone acetylation have the potential to change the effectiveness of antitumour immune responses and therapeutically may have an impact on immunological output.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • Apoptosis / drug effects
  • Azacitidine / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Epigenesis, Genetic / immunology*
  • Genes, MHC Class I*
  • Histones / metabolism
  • Human papillomavirus 16*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / virology
  • Papillomavirus Infections / complications*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Up-Regulation / immunology


  • Enzyme Inhibitors
  • Histones
  • Hydroxamic Acids
  • trichostatin A
  • Azacitidine