Physical Plasma Treatment of Eight Human Cancer Cell Lines Demarcates Upregulation of CD112 as a Common Immunomodulatory Response Element

Cold physical plasma has not only been suggested as novel anticancer but also an immunomodulatory agent. As demonstrated by the Nobel Prize for Medicine and Physiology 2018, immunotherapies are among the most promising strategies to battle cancer by harnessing the power of the immune system. To understand the immunomodulatory effects of cold physical plasma in more detail, we have treated eight human cancer cell lines with the atmospheric pressure argon plasma jet kINPen. Purposefully, noncytotoxic conditions were applied to decipher the genuine oxidative stress response delivered by plasma, and not signaling events associated with cell death. Viability testing confirmed the low toxicity of the chosen treatment regimen. Using multicolor flow cytometry, we have screened the viable cell portion of eight human cancer cell lines against 18 markers of immunomodulation that included both immunostimulatory and immunosuppressive cell surface molecules. From this 18 × 8 matrix data set, an increase greater than 1.5-fold change was observed for CD40 in three cell lines, CD271 in one cell line, and CD112 for all cell lines analyzed. We conclude that with kINPen-plasma-mediated oxidative stress at levels of low cytotoxicity, upregulation of CD112 is a common immunomodulatory response element observed among the eight human cancer cell lines investigated.