Antitumor effects of combined local plasma and anti-PD-1 antibody treatment in a murine colon tumor model

Cold atmospheric-pressure plasma has been suggested to induce antitumor immune responses as a local anticancer treatment. In this study, we investigated whether streamer discharge plasma, a type of cold atmospheric-pressure plasma, enhances the antitumor effects of anti-programmed cell death protein 1 (PD-1) antibody therapy in a murine colon tumor model. Colon26 tumor-bearing mice were randomly assigned to four groups: Control, anti-PD-1 antibody alone, plasma treatment alone and combination treatment with anti-PD-1 antibody and plasma groups. Three independent tumor growth experiments were performed. Under conditions in which anti-PD-1 antibody and plasma treatments alone showed limited effects on tumor growth, the combination treatment delayed tumor growth. Analysis of longitudinal tumor growth curves using a linear mixed model revealed a significant interaction among time, anti-PD-1 antibody treatment and plasma treatment in the integrated dataset, supporting a combined effect on tumor growth. Exploratory flow cytometric analysis showed a numerically lower percentage of F4/80+ macrophage-enriched cells and numerically higher percentages of CD8+ T cell-related populations in the combination group. However, no statistically significant interaction between plasma treatment and anti-PD-1 antibody treatment was detected for any of the flow cytometric parameters. Overall, the pooled analysis supported a combined antitumor effect of local streamer discharge plasma and anti-PD-1 antibody treatment, although the magnitude of the combined effect varied among the three experiments.