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Open AccessArticle

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

1
Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium
2
Plasma, Laser Ablation and Surface Modelling Group, University of Antwerp, 2610 Wilrijk, Belgium
3
Laboratory of Experimental Hematology, University of Antwerp, 2610 Wilrijk, Belgium
4
Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, 9000 Ghent, Belgium
5
Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, 1090 Jette, Belgium
6
Department of Oncology, Multidisciplinary Oncological Center Antwerp, Antwerp University Hospital, 2650 Edegem, Belgium
7
Proteinchemistry, proteomics and epigenetic signaling group, University of Antwerp, 2610 Wilrijk, Belgium
*
Author to whom correspondence should be addressed.
Co-senior authors.
Cancers 2019, 11(10), 1597; https://doi.org/10.3390/cancers11101597
Received: 13 August 2019 / Revised: 16 October 2019 / Accepted: 17 October 2019 / Published: 19 October 2019
(This article belongs to the Special Issue Plasma in Cancer Treatment)
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. View Full-Text
Keywords: pancreatic cancer; pancreatic stellate cells; cold atmospheric plasma; immunogenic cell death; dendritic cells pancreatic cancer; pancreatic stellate cells; cold atmospheric plasma; immunogenic cell death; dendritic cells
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Van Loenhout, J.; Flieswasser, T.; Freire Boullosa, L.; De Waele, J.; Van Audenaerde, J.; Marcq, E.; Jacobs, J.; Lin, A.; Lion, E.; Dewitte, H.; Peeters, M.; Dewilde, S.; Lardon, F.; Bogaerts, A.; Deben, C.; Smits, E. Cold Atmospheric Plasma-Treated PBS Eliminates Immunosuppressive Pancreatic Stellate Cells and Induces Immunogenic Cell Death of Pancreatic Cancer Cells. Cancers 2019, 11, 1597.

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