Medical Gas Plasma Promotes Apoptosis Accompanied by Immunomodulation in Gastrointestinal Tumor Cells

Background/Objectives: Medical plasma is a promising therapeutic approach in oncology due to its ability to generate reactive oxygen and nitrogen species (RONS) and modulate tumor cell viability and phenotype. Therefore, medical plasma could expand the treatment options for highly prevalent or difficult-to-treat cancer entities such as gastrointestinal cancers. Methods: This study investigated the effects of medical plasma generated by the clinically certified argon plasma jet kINPen on two gastrointestinal tumor cell lines (HT-29, MUG-CCArly) with a focus on cytotoxicity, immunomodulation, and redox-dependent mechanisms. Results: Plasma produced a mixture of reactive species under the applied experimental conditions and was able to reduce metabolic activity and cell viability via a redox-dependent induction of apoptosis in both cell lines. Plasma exposure altered the expression of cell-surface markers with potentially immunostimulatory roles such as CD40, CRT, and HMGB1, as well as more immunoregulatory markers like CD47 and PD-L1 (CD274). Additionally, modulated secretion profiles marked by increased pro-inflammatory molecules such as IL-8 and MIP-3a (CCL20) were detected. Conclusion: Overall, congruent but also cell line-dependent responses to plasma treatment were observed that featured a modified immunological phenotype of tumor cells with potentially immunostimulatory but also immunomodulatory aspects, highlighting the potential of medical gas plasma technology as a multimodal therapeutic approach in gastrointestinal oncology.