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.

• MeSH
• Apoptosis drug effects   MeSH
• Azacitidine pharmacology   MeSH
• Epigenesis, Genetic immunology   MeSH
• Neoplasms, Experimental genetics   immunology   virology   MeSH
• Genes, MHC Class I * MeSH
• Histones metabolism   MeSH
• Papillomavirus Infections complications   MeSH
• Enzyme Inhibitors pharmacology   MeSH
• Hydroxamic Acids pharmacology   MeSH
• Humans MeSH
• Human papillomavirus 16 * MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Tumor Cells, Cultured MeSH
• Reverse Transcriptase Polymerase Chain Reaction methods   MeSH
• Antigen Presentation genetics   immunology   MeSH
• Up-Regulation drug effects   genetics   immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Azacitidine MeSH
• Histones MeSH
• Enzyme Inhibitors MeSH
• Hydroxamic Acids MeSH
• trichostatin A MeSH Browser