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Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status
BACKGROUND: Epigenetic mechanisms have important roles in the tumour escape from immune responses, such as in MHC class I downregulation or altered expression of other components involved in antigen presentation. Chemotherapy with DNA methyltransferase inhibitors (DNMTi) can thus influence the tumou...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242529/ https://www.ncbi.nlm.nih.gov/pubmed/22015556 http://dx.doi.org/10.1038/bjc.2011.428 |
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author | Šímová, J Polláková, V Indrová, M Mikyšková, R Bieblová, J Štěpánek, I Bubeník, J Reiniš, M |
author_facet | Šímová, J Polláková, V Indrová, M Mikyšková, R Bieblová, J Štěpánek, I Bubeník, J Reiniš, M |
author_sort | Šímová, J |
collection | PubMed |
description | BACKGROUND: Epigenetic mechanisms have important roles in the tumour escape from immune responses, such as in MHC class I downregulation or altered expression of other components involved in antigen presentation. Chemotherapy with DNA methyltransferase inhibitors (DNMTi) can thus influence the tumour cell interactions with the immune system and their sensitivity to immunotherapy. METHODS: We evaluated the therapeutic effects of the DNMTi 5-azacytidine (5AC) against experimental MHC class I-deficient and -positive tumours. The 5AC therapy was combined with immunotherapy, using a murine model for HPV16-associated tumours. RESULTS: We have demonstrated 5AC additive effects against MHC class I-positive and -deficient tumours when combined with unmethylated CpG oligodeoxynucleotides or with IL-12-producing cellular vaccine. The efficacy of the combined chemoimmunotherapy against originally MHC class I-deficient tumours was partially dependent on the CD8(+)-mediated immune responses. Increased cell surface expression of MHC class I cell molecules, associated with upregulation of the antigen-presenting machinery-related genes, as well as of genes encoding selected components of the IFNγ-signalling pathway in tumours explanted from 5AC-treated animals, were observed. CONCLUSION: Our data suggest that chemotherapy of MHC class I-deficient tumours with 5AC combined with immunotherapy is an attractive setting in the treatment of MHC class I-deficient tumours. |
format | Online Article Text |
id | pubmed-3242529 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-32425292012-11-08 Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status Šímová, J Polláková, V Indrová, M Mikyšková, R Bieblová, J Štěpánek, I Bubeník, J Reiniš, M Br J Cancer Translational Therapeutics BACKGROUND: Epigenetic mechanisms have important roles in the tumour escape from immune responses, such as in MHC class I downregulation or altered expression of other components involved in antigen presentation. Chemotherapy with DNA methyltransferase inhibitors (DNMTi) can thus influence the tumour cell interactions with the immune system and their sensitivity to immunotherapy. METHODS: We evaluated the therapeutic effects of the DNMTi 5-azacytidine (5AC) against experimental MHC class I-deficient and -positive tumours. The 5AC therapy was combined with immunotherapy, using a murine model for HPV16-associated tumours. RESULTS: We have demonstrated 5AC additive effects against MHC class I-positive and -deficient tumours when combined with unmethylated CpG oligodeoxynucleotides or with IL-12-producing cellular vaccine. The efficacy of the combined chemoimmunotherapy against originally MHC class I-deficient tumours was partially dependent on the CD8(+)-mediated immune responses. Increased cell surface expression of MHC class I cell molecules, associated with upregulation of the antigen-presenting machinery-related genes, as well as of genes encoding selected components of the IFNγ-signalling pathway in tumours explanted from 5AC-treated animals, were observed. CONCLUSION: Our data suggest that chemotherapy of MHC class I-deficient tumours with 5AC combined with immunotherapy is an attractive setting in the treatment of MHC class I-deficient tumours. Nature Publishing Group 2011-11-08 2011-10-20 /pmc/articles/PMC3242529/ /pubmed/22015556 http://dx.doi.org/10.1038/bjc.2011.428 Text en Copyright © 2011 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Translational Therapeutics Šímová, J Polláková, V Indrová, M Mikyšková, R Bieblová, J Štěpánek, I Bubeník, J Reiniš, M Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status |
title | Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status |
title_full | Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status |
title_fullStr | Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status |
title_full_unstemmed | Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status |
title_short | Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status |
title_sort | immunotherapy augments the effect of 5-azacytidine on hpv16-associated tumours with different mhc class i-expression status |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242529/ https://www.ncbi.nlm.nih.gov/pubmed/22015556 http://dx.doi.org/10.1038/bjc.2011.428 |
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