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Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells

SIMPLE SUMMARY: Natural killer (NK)-cells are known to have antitumor potential. Cold physical plasma generates ROS exogenously to be utilized as a novel anticancer agent, especially in skin cancer. However, it is unknown whether plasma-treated skin cancer cells promote or inhibit NK-cell-mediated t...

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Autores principales: Clemen, Ramona, Heirman, Pepijn, Lin, Abraham, Bogaerts, Annemie, Bekeschus, Sander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761052/
https://www.ncbi.nlm.nih.gov/pubmed/33265951
http://dx.doi.org/10.3390/cancers12123575
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author Clemen, Ramona
Heirman, Pepijn
Lin, Abraham
Bogaerts, Annemie
Bekeschus, Sander
author_facet Clemen, Ramona
Heirman, Pepijn
Lin, Abraham
Bogaerts, Annemie
Bekeschus, Sander
author_sort Clemen, Ramona
collection PubMed
description SIMPLE SUMMARY: Natural killer (NK)-cells are known to have antitumor potential. Cold physical plasma generates ROS exogenously to be utilized as a novel anticancer agent, especially in skin cancer. However, it is unknown whether plasma-treated skin cancer cells promote or inhibit NK-cell-mediated toxicity. To this end, we analyzed NK-cell-activating receptors on plasma-treated skin cancer cells and demonstrated an enhanced NK-cell activity augmenting tumor cell death upon plasma treatment. ABSTRACT: Skin cancers have the highest prevalence of all human cancers, with the most lethal forms being squamous cell carcinoma and malignant melanoma. Besides the conventional local treatment approaches like surgery and radiotherapy, cold physical plasmas are emerging anticancer tools. Plasma technology is used as a therapeutic agent by generating reactive oxygen species (ROS). Evidence shows that inflammation and adaptive immunity are involved in cancer-reducing effects of plasma treatment, but the role of innate immune cells is still unclear. Natural killer (NK)-cells interact with target cells via activating and inhibiting surface receptors and kill in case of dominating activating signals. In this study, we investigated the effect of cold physical plasma (kINPen) on two skin cancer cell lines (A375 and A431), with non-malignant HaCaT keratinocytes as control, and identified a plasma treatment time-dependent toxicity that was more pronounced in the cancer cells. Plasma treatment also modulated the expression of activating and inhibiting receptors more profoundly in skin cancer cells compared to HaCaT cells, leading to significantly higher NK-cell killing rates in the tumor cells. Together with increased pro-inflammatory mediators such as IL-6 and IL-8, we conclude that plasma treatment spurs stress responses in skin cancer cells, eventually augmenting NK-cell activity.
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spelling pubmed-77610522020-12-26 Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells Clemen, Ramona Heirman, Pepijn Lin, Abraham Bogaerts, Annemie Bekeschus, Sander Cancers (Basel) Article SIMPLE SUMMARY: Natural killer (NK)-cells are known to have antitumor potential. Cold physical plasma generates ROS exogenously to be utilized as a novel anticancer agent, especially in skin cancer. However, it is unknown whether plasma-treated skin cancer cells promote or inhibit NK-cell-mediated toxicity. To this end, we analyzed NK-cell-activating receptors on plasma-treated skin cancer cells and demonstrated an enhanced NK-cell activity augmenting tumor cell death upon plasma treatment. ABSTRACT: Skin cancers have the highest prevalence of all human cancers, with the most lethal forms being squamous cell carcinoma and malignant melanoma. Besides the conventional local treatment approaches like surgery and radiotherapy, cold physical plasmas are emerging anticancer tools. Plasma technology is used as a therapeutic agent by generating reactive oxygen species (ROS). Evidence shows that inflammation and adaptive immunity are involved in cancer-reducing effects of plasma treatment, but the role of innate immune cells is still unclear. Natural killer (NK)-cells interact with target cells via activating and inhibiting surface receptors and kill in case of dominating activating signals. In this study, we investigated the effect of cold physical plasma (kINPen) on two skin cancer cell lines (A375 and A431), with non-malignant HaCaT keratinocytes as control, and identified a plasma treatment time-dependent toxicity that was more pronounced in the cancer cells. Plasma treatment also modulated the expression of activating and inhibiting receptors more profoundly in skin cancer cells compared to HaCaT cells, leading to significantly higher NK-cell killing rates in the tumor cells. Together with increased pro-inflammatory mediators such as IL-6 and IL-8, we conclude that plasma treatment spurs stress responses in skin cancer cells, eventually augmenting NK-cell activity. MDPI 2020-11-30 /pmc/articles/PMC7761052/ /pubmed/33265951 http://dx.doi.org/10.3390/cancers12123575 Text en © 2020 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
Clemen, Ramona
Heirman, Pepijn
Lin, Abraham
Bogaerts, Annemie
Bekeschus, Sander
Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells
title Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells
title_full Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells
title_fullStr Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells
title_full_unstemmed Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells
title_short Physical Plasma-Treated Skin Cancer Cells Amplify Tumor Cytotoxicity of Human Natural Killer (NK) Cells
title_sort physical plasma-treated skin cancer cells amplify tumor cytotoxicity of human natural killer (nk) cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761052/
https://www.ncbi.nlm.nih.gov/pubmed/33265951
http://dx.doi.org/10.3390/cancers12123575
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