Toxicity and Immunogenicity in Murine Melanoma following Exposure to Physical Plasma-Derived Oxidants.

Sander Bekeschus,Rajesh Kumar Gandhirajan,Bob Fregin,Klaus-Dieter Weltmann,Katrin Rödder,Maxi Lippert,Kristian Wende,Oliver Otto,Anke Schmidt

doi:10.1155/2017/4396467

Sander Bekeschus, Rajesh Kumar Gandhirajan + Show 7 more

Open Access

https://doi.org/10.1155/2017/4396467

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Abstract

Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has been achieved by antitumor chemo- and radiotherapy. These modalities involve the generation of reactive oxygen and nitrogen species, affecting cellular viability, migration, and immunogenicity. Such species are also created by cold physical plasma, an ionized gas capable of redox modulating cells and tissues without thermal damage. Cold plasma has been suggested for anticancer therapy. Here, melanoma cell toxicity, motility, and immunogenicity of murine metastatic melanoma cells were investigated following plasma exposure in vitro. Cells were oxidized by plasma, leading to decreased metabolic activity and cell death. Moreover, plasma decelerated melanoma cell growth, viability, and cell cycling. This was accompanied by increased cellular stiffness and upregulation of zonula occludens 1 protein in the cell membrane. Importantly, expression levels of immunogenic cell surface molecules such as major histocompatibility complex I, calreticulin, and melanocortin receptor 1 were significantly increased in response to plasma. Finally, plasma treatment significantly decreased the release of vascular endothelial growth factor, a molecule with importance in angiogenesis. Altogether, these results suggest beneficial toxicity of cold plasma in murine melanomas with a concomitant immunogenicity of potential interest in oncology.

Highlights

With over 70,000 new incidences and 10,000 deaths annually in the U.S alone, melanoma is a highly prevalent type of cancer [1]
Mitochondrial-derived reactive oxygen species (ROS) and reactive nitrogen species (RNS) and subsequent oxidative events seem to contribute to some molecular Immunogenic cell death (ICD) events following chemo- and radiotherapy [11]
In cells loaded with H2-DCF-DA, plasma treatment increased total fluorescence in B16 melanoma cells compared to untreated controls (Figure 1(a))

Summary

Introduction

With over 70,000 new incidences and 10,000 deaths annually in the U.S alone, melanoma is a highly prevalent type of cancer [1]. Advances have been made in melanoma therapy in the past decade but stage IV survival of nonresponder patients is still poor [2]. This owes partly to melanomas having the highest mutational burden but at the same time having the most neoantigens among all types of cancers in humans [3]. Similar to other types of cancer, the majority of patients die due to metastasis spreading throughout the body [4]. This requires an understanding of cellular behavior and motility in response to therapy [5]. Mitochondrial-derived reactive oxygen species (ROS) and reactive nitrogen species (RNS) and subsequent oxidative events seem to contribute to some molecular ICD events following chemo- and radiotherapy [11]

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