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Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stella...

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Autores principales: Van Loenhout, Jinthe, Flieswasser, Tal, Freire Boullosa, Laurie, De Waele, Jorrit, Van Audenaerde, Jonas, Marcq, Elly, Jacobs, Julie, Lin, Abraham, Lion, Eva, Dewitte, Heleen, Peeters, Marc, Dewilde, Sylvia, Lardon, Filip, Bogaerts, Annemie, Deben, Christophe, Smits, Evelien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826654/
https://www.ncbi.nlm.nih.gov/pubmed/31635070
http://dx.doi.org/10.3390/cancers11101597
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author Van Loenhout, Jinthe
Flieswasser, Tal
Freire Boullosa, Laurie
De Waele, Jorrit
Van Audenaerde, Jonas
Marcq, Elly
Jacobs, Julie
Lin, Abraham
Lion, Eva
Dewitte, Heleen
Peeters, Marc
Dewilde, Sylvia
Lardon, Filip
Bogaerts, Annemie
Deben, Christophe
Smits, Evelien
author_facet Van Loenhout, Jinthe
Flieswasser, Tal
Freire Boullosa, Laurie
De Waele, Jorrit
Van Audenaerde, Jonas
Marcq, Elly
Jacobs, Julie
Lin, Abraham
Lion, Eva
Dewitte, Heleen
Peeters, Marc
Dewilde, Sylvia
Lardon, Filip
Bogaerts, Annemie
Deben, Christophe
Smits, Evelien
author_sort Van Loenhout, Jinthe
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stellate cells (PSCs). Therefore, new therapeutic strategies are needed to tackle both the immunosuppressive PSC and pancreatic cancer cells (PCCs). Recently, physical cold atmospheric plasma consisting of reactive oxygen and nitrogen species has emerged as a novel treatment option for cancer. In this study, we investigated the cytotoxicity of plasma-treated phosphate-buffered saline (pPBS) using three PSC lines and four PCC lines and examined the immunogenicity of the induced cell death. We observed a decrease in the viability of PSC and PCC after pPBS treatment, with a higher efficacy in the latter. Two PCC lines expressed and released damage-associated molecular patterns characteristic of the induction of immunogenic cell death (ICD). In addition, pPBS-treated PCC were highly phagocytosed by dendritic cells (DCs), resulting in the maturation of DC. This indicates the high potential of pPBS to trigger ICD. In contrast, pPBS induced no ICD in PSC. In general, pPBS treatment of PCCs and PSCs created a more immunostimulatory secretion profile (higher TNF-α and IFN-γ, lower TGF-β) in coculture with DC. Altogether, these data show that plasma treatment via pPBS has the potential to induce ICD in PCCs and to reduce the immunosuppressive tumor microenvironment created by PSCs. Therefore, these data provide a strong experimental basis for further in vivo validation, which might potentially open the way for more successful combination strategies with immunotherapy for PDAC.
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spelling pubmed-68266542019-11-18 Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells Van Loenhout, Jinthe Flieswasser, Tal Freire Boullosa, Laurie De Waele, Jorrit Van Audenaerde, Jonas Marcq, Elly Jacobs, Julie Lin, Abraham Lion, Eva Dewitte, Heleen Peeters, Marc Dewilde, Sylvia Lardon, Filip Bogaerts, Annemie Deben, Christophe Smits, Evelien Cancers (Basel) Article Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low response to treatment and a five-year survival rate below 5%. The ineffectiveness of treatment is partly because of an immunosuppressive tumor microenvironment, which comprises tumor-supportive pancreatic stellate cells (PSCs). Therefore, new therapeutic strategies are needed to tackle both the immunosuppressive PSC and pancreatic cancer cells (PCCs). Recently, physical cold atmospheric plasma consisting of reactive oxygen and nitrogen species has emerged as a novel treatment option for cancer. In this study, we investigated the cytotoxicity of plasma-treated phosphate-buffered saline (pPBS) using three PSC lines and four PCC lines and examined the immunogenicity of the induced cell death. We observed a decrease in the viability of PSC and PCC after pPBS treatment, with a higher efficacy in the latter. Two PCC lines expressed and released damage-associated molecular patterns characteristic of the induction of immunogenic cell death (ICD). In addition, pPBS-treated PCC were highly phagocytosed by dendritic cells (DCs), resulting in the maturation of DC. This indicates the high potential of pPBS to trigger ICD. In contrast, pPBS induced no ICD in PSC. In general, pPBS treatment of PCCs and PSCs created a more immunostimulatory secretion profile (higher TNF-α and IFN-γ, lower TGF-β) in coculture with DC. Altogether, these data show that plasma treatment via pPBS has the potential to induce ICD in PCCs and to reduce the immunosuppressive tumor microenvironment created by PSCs. Therefore, these data provide a strong experimental basis for further in vivo validation, which might potentially open the way for more successful combination strategies with immunotherapy for PDAC. MDPI 2019-10-19 /pmc/articles/PMC6826654/ /pubmed/31635070 http://dx.doi.org/10.3390/cancers11101597 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Van Loenhout, Jinthe
Flieswasser, Tal
Freire Boullosa, Laurie
De Waele, Jorrit
Van Audenaerde, Jonas
Marcq, Elly
Jacobs, Julie
Lin, Abraham
Lion, Eva
Dewitte, Heleen
Peeters, Marc
Dewilde, Sylvia
Lardon, Filip
Bogaerts, Annemie
Deben, Christophe
Smits, Evelien
Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells
title Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells
title_full Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells
title_fullStr Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells
title_full_unstemmed Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells
title_short Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells
title_sort cold atmospheric plasma-treated pbs eliminates immunosuppressive pancreatic stellate cells and induces immunogenic cell death of pancreatic cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826654/
https://www.ncbi.nlm.nih.gov/pubmed/31635070
http://dx.doi.org/10.3390/cancers11101597
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