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search.filters.applied.f.access: openAccess × Author: Clemen, Ramona × DDC: 610 × Subject: ROS ×

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    Physical plasma-treated skin cancer cells amplify tumor cytotoxicity of human natural killer (NK) cells
    (Basel : MDPI AG, 2020) Clemen, Ramona; Heirman, Pepijn; Lin, Abraham; Bogaerts, Annemie; Bekeschus, Sander
    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. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    Gas Plasma Protein Oxidation Increases Immunogenicity and Human Antigen-Presenting Cell Maturation and Activation
    (Basel : MDPI, 2022) Clemen, Ramona; Arlt, Kevin; von Woedtke, Thomas; Bekeschus, Sander
    Protein vaccines rely on eliciting immune responses. Inflammation is a prerequisite for immune responses to control infection and cancer but is also associated with disease onset. Reactive oxygen species (ROSs) are central during inflammation and are capable of inducing non-enzymatic oxidative protein modifications (oxMods) associated with chronic disease, which alter the functionality or immunogenicity of proteins that are relevant in cancer immunotherapy. Specifically, antigen-presenting cells (APCs) take up and degrade extracellular native and oxidized proteins to induce adaptive immune responses. However, it is less clear how oxMods alter the protein’s immunogenicity, especially in inflammation-related short-lived reactive species. Gas plasma technology simultaneously generates a multitude of ROSs to modify protein antigens in a targeted and controlled manner to study the immunogenicity of oxMods. As model proteins relevant to chronic inflammation and cancer, we used gas plasma-treated insulin and CXCL8. We added those native or oxidized proteins to human THP-1 monocytes or primary monocyte-derived cells (moDCs). Both oxidized proteins caused concentration-independent maturation phenotype alterations in moDCs and THP-1 cells concerning surface marker expression and chemokine and cytokine secretion profiles. Interestingly, concentration-matched H2O2-treated proteins did not recapitulate the effects of gas plasma, suggesting sufficiently short diffusion distances for the short-lived reactive species to modify proteins. Our data provide evidence of dendric cell maturation and activation upon exposure to gas plasma- but not H2O2-modified model proteins. The biological consequences of these findings need to be elucidated in future inflammation and cancer disease models.