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Epigenetic modulation of antitumor immunity for improved cancer immunotherapy
Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also in the activation, differentiation and effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics in immune cells impacting immune cell fate and fu...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691037/ https://www.ncbi.nlm.nih.gov/pubmed/34930302 http://dx.doi.org/10.1186/s12943-021-01464-x |
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author | Dai, Enyong Zhu, Zhi Wahed, Shudipto Qu, Zhaoxia Storkus, Walter J. Guo, Zong Sheng |
author_facet | Dai, Enyong Zhu, Zhi Wahed, Shudipto Qu, Zhaoxia Storkus, Walter J. Guo, Zong Sheng |
author_sort | Dai, Enyong |
collection | PubMed |
description | Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also in the activation, differentiation and effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics in immune cells impacting immune cell fate and functionality, and the immunogenicity of cancer cells. Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 and STING, are regulated via epigenetic mechanisms in immune or/and cancer cells, as are immune checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by immune cells and tumor-associated stromal cells. Thus, therapeutic strategies implementing epigenetic modulating drugs are expected to significantly impact the tumor microenvironment (TME) by promoting transcriptional and metabolic reprogramming in local immune cell populations, resulting in inhibition of immunosuppressive cells (MDSCs and Treg) and the activation of anti-tumor T effector cells, professional antigen presenting cells (APC), as well as cancer cells which can serve as non-professional APC. In the latter instance, epigenetic modulating agents may coordinately promote tumor immunogenicity by inducing de novo expression of transcriptionally repressed tumor-associated antigens, increasing expression of neoantigens and MHC processing/presentation machinery, and activating tumor immunogenic cell death (ICD). ICD provides a rich source of immunogens for anti-tumor T cell cross-priming and sensitizing cancer cells to interventional immunotherapy. In this way, epigenetic modulators may be envisioned as effective components in combination immunotherapy approaches capable of mediating superior therapeutic efficacy. |
format | Online Article Text |
id | pubmed-8691037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86910372021-12-23 Epigenetic modulation of antitumor immunity for improved cancer immunotherapy Dai, Enyong Zhu, Zhi Wahed, Shudipto Qu, Zhaoxia Storkus, Walter J. Guo, Zong Sheng Mol Cancer Review Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also in the activation, differentiation and effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics in immune cells impacting immune cell fate and functionality, and the immunogenicity of cancer cells. Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 and STING, are regulated via epigenetic mechanisms in immune or/and cancer cells, as are immune checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by immune cells and tumor-associated stromal cells. Thus, therapeutic strategies implementing epigenetic modulating drugs are expected to significantly impact the tumor microenvironment (TME) by promoting transcriptional and metabolic reprogramming in local immune cell populations, resulting in inhibition of immunosuppressive cells (MDSCs and Treg) and the activation of anti-tumor T effector cells, professional antigen presenting cells (APC), as well as cancer cells which can serve as non-professional APC. In the latter instance, epigenetic modulating agents may coordinately promote tumor immunogenicity by inducing de novo expression of transcriptionally repressed tumor-associated antigens, increasing expression of neoantigens and MHC processing/presentation machinery, and activating tumor immunogenic cell death (ICD). ICD provides a rich source of immunogens for anti-tumor T cell cross-priming and sensitizing cancer cells to interventional immunotherapy. In this way, epigenetic modulators may be envisioned as effective components in combination immunotherapy approaches capable of mediating superior therapeutic efficacy. BioMed Central 2021-12-20 /pmc/articles/PMC8691037/ /pubmed/34930302 http://dx.doi.org/10.1186/s12943-021-01464-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Review Dai, Enyong Zhu, Zhi Wahed, Shudipto Qu, Zhaoxia Storkus, Walter J. Guo, Zong Sheng Epigenetic modulation of antitumor immunity for improved cancer immunotherapy |
title | Epigenetic modulation of antitumor immunity for improved cancer immunotherapy |
title_full | Epigenetic modulation of antitumor immunity for improved cancer immunotherapy |
title_fullStr | Epigenetic modulation of antitumor immunity for improved cancer immunotherapy |
title_full_unstemmed | Epigenetic modulation of antitumor immunity for improved cancer immunotherapy |
title_short | Epigenetic modulation of antitumor immunity for improved cancer immunotherapy |
title_sort | epigenetic modulation of antitumor immunity for improved cancer immunotherapy |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8691037/ https://www.ncbi.nlm.nih.gov/pubmed/34930302 http://dx.doi.org/10.1186/s12943-021-01464-x |
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