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
• apoptóza účinky léků   MeSH
• azacytidin farmakologie   MeSH
• epigeneze genetická imunologie   MeSH
• experimentální nádory genetika   imunologie   virologie   MeSH
• geny MHC třídy I * MeSH
• histony metabolismus   MeSH
• infekce papilomavirem komplikace   MeSH
• inhibitory enzymů farmakologie   MeSH
• kyseliny hydroxamové farmakologie   MeSH
• lidé MeSH
• lidský papilomavirus 16 * MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   MeSH
• prezentace antigenu genetika   imunologie   MeSH
• upregulace účinky léků   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• azacytidin MeSH
• histony MeSH
• inhibitory enzymů MeSH
• kyseliny hydroxamové MeSH
• trichostatin A MeSH Prohlížeč