  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.
