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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-...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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