Plasma-Derived Oxidants And The Modulation Of Immunsuppression In Melanoma

Abstract

Many diseases are based on dysregulated immune responses. For instance, cancers benefit from immunosuppression [1]. Tumor cells initiate tolerance mechanisms e.g. by expression of inhibitory surface molecules, blunting antitumor immune responses. Similar receptors are often upregulated in immunosuppressive immune cells in the tumor microenvironment as well [2]. These receptors can contribute to the tumor growth and progression and are associated with a poor prognosis [3]. Reactive oxygen species were identified to be involved in the differentiation of hematopoietic lineages and in the regulation of the tumor environment [4, 5]. At the same time, cold physical plasmas were found to be a promising approach in cancer therapy and immunomodulation [6]. Therefore, plasma-derived oxidants may contribute to alter the immunosuppressive potential of immune or cancer cells. Treatment of melanoma and immune cells by plasma was followed by flow cytometric measurements of key immunomodulatory surface markers and their immunosuppressive secretion products. Moreover, immunosuppressive cells release distinct types and amounts of chemokines or cytokines compared to the immune active cells. With the help of these molecules, immunosuppression is spread in the tumor environment. We analyzed the culture supernatants of patient-derived skin cancer samples treated ex vivo with cold physical plasma. With regard to the immunosuppression, distinct cytokine profiles were shown in plasma-treated clinical samples compared to the controls. In addition, in vitro co-culture assays with melanoma and immune cells verified the potential of plasma in modulating the immunosuppression. This study illustrates the importance and potential of utilizes plasmas to manipulate the redox environment for tumor immune control.