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HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma
Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962361/ https://www.ncbi.nlm.nih.gov/pubmed/35203582 http://dx.doi.org/10.3390/biomedicines10020373 |
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author | Gong, Wenjie Wang, Lei Schubert, Maria-Luisa Kleist, Christian Neuber, Brigitte Wang, Sanmei Yang, Mingya Hückelhoven-Krauss, Angela Wu, Depei Schmitt, Anita Müller-Tidow, Carsten Shiku, Hiroshi Schmitt, Michael Sellner, Leopold |
author_facet | Gong, Wenjie Wang, Lei Schubert, Maria-Luisa Kleist, Christian Neuber, Brigitte Wang, Sanmei Yang, Mingya Hückelhoven-Krauss, Angela Wu, Depei Schmitt, Anita Müller-Tidow, Carsten Shiku, Hiroshi Schmitt, Michael Sellner, Leopold |
author_sort | Gong, Wenjie |
collection | PubMed |
description | Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-testis antigen NY-ESO-1 using histone deacetylase inhibitors (HDACis). In this study, the ex vivo effect of combining NY-ESO-1-specific T cells with the clinically approved pan HDACis panobinostat or vorionstat was investigated. Our data demonstrated that STS cells were sensitive to HDACis. Administration of HDACi prior to NY-ESO-1-specific T cells exerted enhanced lysis against the NY-ESO-1+ STS cell line SW982. This correlated with an increase in the NY-ESO-1 and HLA-ABC expression of SW982 cells, as well as increased CD25 expression on NY-ESO-1-specific T cells. Furthermore, the immune reactivity of NY-ESO-1-specific CD8+ T cells in terms of cytokine release was enhanced by HDACis. In summary, pretreatment with HDACis represents a potential means of enhancing the cytotoxic efficacy of NY-ESO-1-specific T cells against NY-ESO-1-positive STS. |
format | Online Article Text |
id | pubmed-8962361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89623612022-03-30 HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma Gong, Wenjie Wang, Lei Schubert, Maria-Luisa Kleist, Christian Neuber, Brigitte Wang, Sanmei Yang, Mingya Hückelhoven-Krauss, Angela Wu, Depei Schmitt, Anita Müller-Tidow, Carsten Shiku, Hiroshi Schmitt, Michael Sellner, Leopold Biomedicines Article Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-testis antigen NY-ESO-1 using histone deacetylase inhibitors (HDACis). In this study, the ex vivo effect of combining NY-ESO-1-specific T cells with the clinically approved pan HDACis panobinostat or vorionstat was investigated. Our data demonstrated that STS cells were sensitive to HDACis. Administration of HDACi prior to NY-ESO-1-specific T cells exerted enhanced lysis against the NY-ESO-1+ STS cell line SW982. This correlated with an increase in the NY-ESO-1 and HLA-ABC expression of SW982 cells, as well as increased CD25 expression on NY-ESO-1-specific T cells. Furthermore, the immune reactivity of NY-ESO-1-specific CD8+ T cells in terms of cytokine release was enhanced by HDACis. In summary, pretreatment with HDACis represents a potential means of enhancing the cytotoxic efficacy of NY-ESO-1-specific T cells against NY-ESO-1-positive STS. MDPI 2022-02-03 /pmc/articles/PMC8962361/ /pubmed/35203582 http://dx.doi.org/10.3390/biomedicines10020373 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gong, Wenjie Wang, Lei Schubert, Maria-Luisa Kleist, Christian Neuber, Brigitte Wang, Sanmei Yang, Mingya Hückelhoven-Krauss, Angela Wu, Depei Schmitt, Anita Müller-Tidow, Carsten Shiku, Hiroshi Schmitt, Michael Sellner, Leopold HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma |
title | HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma |
title_full | HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma |
title_fullStr | HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma |
title_full_unstemmed | HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma |
title_short | HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma |
title_sort | hdac inhibition for optimized cellular immunotherapy of ny-eso-1-positive soft tissue sarcoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962361/ https://www.ncbi.nlm.nih.gov/pubmed/35203582 http://dx.doi.org/10.3390/biomedicines10020373 |
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