Enhancing Innate and Adaptive Immune Systems by Cold Atmospheric Plasma (CAP) and Its Antitumor Immunity

Abstract: Cold atmospheric plasma (CAP) is a near room temperature ionized gas, generated under non-equilibrium discharge conditions. Here we show that a short exposure of rat peritoneal exudate macrophages and T-cells to CAP in vitro, triggered an inflammatory phenotype leading to better antigen-presenting and effector cell function respectively. Different from previous studies mainly using immortalized cell lines, both macrophage and T-cells in this study were primary cells isolated from mice. Furthermore, ex-vivo exposure of T-cells to CAP, followed by their adoptive transfer into tumor-bearing mice resulted in a strong antitumor effect in vivo. Mechanistically, CAP seems to disrupt tolerogenic pathways leading to enhanced production of pro-inflammatory cytokines while limiting the production of anti-inflammatory cytokines and the expression of inhibitory molecules such as programmed death-ligand 1 (PD-L1). CAP represents therefore a novel, non-toxic and easy to deliver technology to augment the function of immune cells and enhance antitumor responses when used as a component of T-cell adoptive immunotherapies strategies or, potentially in combination with other cancer immunotherapeutic approaches.