Gas Plasma-Treated Prostate Cancer Cells Augment Myeloid Cell Activity and Cytotoxicity

Abstract

Despite recent improvements in cancer treatment, with many of them being related to foster antitumor immunity, tumor-related deaths continue to be high. Novel avenues are needed to complement existing therapeutic strategies in oncology. Medical gas plasma technology recently gained attention due to its antitumor activity. Gas plasmas act via the local deposition of a plethora of reactive oxygen species (ROS) that promote the oxidative cancer cell death. The immunological consequences of plasma-mediated tumor cell death are only poorly understood, however. To this end, we exposed two prostate cancer cell lines (LNCaP, PC3) to gas plasma in vitro, and investigated the immunomodulatory effects of the supernatants in as well as of direct co-culturing with two human myeloid cell lines (THP-1, HL-60). After identifying the cytotoxic action of the kINPen plasma jet, the supernatants of plasma-treated prostate cancer cells modulated myeloid cell-related mitochondrial ROS production and their metabolic activity, proliferation, surface marker expression, and cytokine release. Direct co-culture amplified differentiation-like surface marker expression in myeloid cells and promoted their antitumor-toxicity in the gas plasma over the untreated control conditions. The results suggest that gas plasma-derived ROS not only promote prostate cancer cell death but also augment myeloid cell activity and cytotoxicity.

Critical Analysis of Non-Thermal Plasma-Driven Modulation of Immune Cells from Clinical Perspective

“…Indeed, wounds and skin diseases represent the majority of pathological conditions where the side effects of NTP were assessed ( Table 2 ). However, NTP treatment endeavors to attain different clinical applications (not only wound healing) [ 4 , 18 , 19 ]. Therefore, studies on potential side effects and those related to treatment complications should be scaled up.…”

“…In the last two decades, the research has shown that non-thermal plasma (also known as cold atmospheric plasma or non-equilibrium atmospheric pressure plasma) has significant potential in various biomedical applications [ 3 , 4 , 5 ]. Indeed, non-thermal plasma (NTP) has emerged as a promising tool for the sterilization of medical equipment [ 6 , 7 , 8 ], wound healing [ 9 , 10 ], bacteria eradication [ 11 , 12 , 13 , 14 ], dental hygiene [ 6 , 15 ], blood coagulation [ 16 ], angiogenesis suppression [ 17 ], cancer treatment [ 4 , 18 , 19 ], and food decontamination [ 20 , 21 ]. It is worth noting here that, while some studies show angiogenesis suppression [ 17 ], others describe accelerated angiogenesis by NTP [ 10 , 22 ].…”

Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen

“…The relevance of this cross-species approach is underlined by DC activation being triggered via the binding of immune-stimulatory molecules to evolutionarily conserved pattern recognition receptors such as toll-like receptors that only differ slightly in structure and subsequent signaling pathways across species 80,81 . Effects of plasma-derived species on myeloid cells such as DCs [82][83][84] , macrophages 85,86 as well as innate lymphocytes 87 was suggested before already.To gain evidence of the tumor treatment regimes' ability to induce DC maturation, we characterized the expression of reliable maturation www.nature.com/scientificreports/ markers on DCs. We found kINPen but not V jet plasma-treated tumor cells to promote dendritic cell maturation and tumor cell phagocytosis.…”

Argon Plasma Exposure Augments Costimulatory Ligands and Cytokine Release in Human Monocyte-Derived Dendritic Cells

“…In some experiments, kinetic readings were performed on the device by preheating it up to 37 °C for 1 h, adding additional double-distilled water to the outer rim of the Eppendorf 24-well plate as evaporation shield protection, and continuously supplying 5% CO 2 to the plate reader using the Gas Control Module (GCM; Tecan, Männedorf, Switzerland). For analyzing the concentration of cytokines in cell culture supernatants, the LEGENDplex (BioLegend, Amsterdam, The Netherlands) multiplex bead technology was used as recently described [ 65 ]. Briefly, supernatants were collected in 96-well plates and stored at −20 °C for longitudinal analysis.…”