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Author: Moritz, Juliane × Author: von Woedtke, Thomas × End date: 2024 × Start date: 2020 ×

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    Ex Vivo Exposure of Human Melanoma Tissue to Cold Physical Plasma Elicits Apoptosis and Modulates Inflammation
    (Basel : MDPI, 2020) Bekeschus, Sander; Moritz, Juliane; Helfrich, Iris; Boeckmann, Lars; Weltmann, Klaus-Dieter; Emmert, Steffen; Metelmann, Hans-Robert; Stoffels, Ingo; von Woedtke, Thomas
    Cutaneous melanoma is the most aggressive type of skin cancer with a not-sufficient clinical outcome. High tumor mutation rates often hamper a remedial treatment, creating the need for palliative care in many patients. To reduce pain and burden, local palliation often includes cryo-ablation, immunotherapy via injection of IL2, or electrochemotherapy. Yet, a fraction of patients and lesions do not respond to those therapies. To reach even these resistances in a redox-mediated way, we treated skin biopsies from human melanoma ex vivo with cold physical plasma (kINPen MED plasma jet). This partially ionized gas generates a potent mixture of reactive oxygen species (ROS). Physical plasmas have been shown to be potent antitumor agents in preclinical melanoma and clinical head and neck cancer research. The innovation of this technology lies in its ease-of-use without anesthesia, as the “cold” plasma temperature of the kINPen MED does not exceed 37 °C. In metastatic melanoma skin biopsies from six patients, we identified a marked increase of apoptosis with plasma treatment ex vivo. This had an impact on the chemokine/cytokine profile of the cultured biopsies, e.g., three of six patient-derived biopsy supernatants showed an apparent decrease in VEGF compared to non-plasma treated specimens. Moreover, the baseline release levels of 24 chemokines/cytokines investigated may serve as a useful tool for future research on melanoma skin biopsy treatments. Our findings suggest a clinically useful role of cold physical plasma therapy in palliation of cutaneous melanoma lesions, possibly in a combinatory setting with other immune therapies.
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    xCT (SLC7A11) expression confers intrinsic resistance to physical plasma treatment in tumor cells
    (Amsterdam [u.a.] : Elsevier, 2020) Bekeschus, Sander; Eisenmann, Sebastian; Sagwal, Sanjeev Kumar; Bodnar, Yana; Moritz, Juliane; Poschkamp, Broder; Stoffels, Ingo; Emmert, Steffen; Madesh, Muniswamy; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Gandhirajan, Rajesh Kumar
    Cold physical plasma is a partially ionized gas investigated as a new anticancer tool in selectively targeting cancer cells in monotherapy or in combination with therapeutic agents. Here, we investigated the intrinsic resistance mechanisms of tumor cells towards physical plasma treatment. When analyzing the dose-response relationship to cold plasma-derived oxidants in 11 human cancer cell lines, we identified four 'resistant' and seven 'sensitive' cell lines. We observed stable intracellular glutathione levels following plasma treatment only in the 'resistant' cell lines indicative of altered antioxidant mechanisms. Assessment of proteins involved in GSH metabolism revealed cystine-glutamate antiporter xCT (SLC7A11) to be significantly more abundant in the 'resistant' cell lines as compared to 'sensitive' cell lines. This decisive role of xCT was confirmed by pharmacological and genetic inhibition, followed by cold physical plasma treatment. Finally, microscopy analysis of ex vivo plasma-treated human melanoma punch biopsies suggested a correlation between apoptosis and basal xCT protein abundance. Taken together, our results demonstrate that xCT holds the potential as a biomarker predicting the sensitivity of tumor cells towards plasma treatment.