Differential Effect of Non-Thermal Plasma RONS on Two Human Leukemic Cell Populations

SIMPLE SUMMARY: As the number of investigations into the use of non-thermal plasma (NTP) for cancer treatment expands, it is becoming apparent that susceptibility of different cancer cells to NTP varies. We hypothesized that such differences could be attributed to the cell type-dependent interactions between NTP-generated reactive oxygen and nitrogen species (RONS) and the target cells. To test this hypothesis, we examined how two different human leukemic cell lines—Jurkat T lymphocytes and THP-1 monocytes—influence hydrogen peroxide and nitrite content in media after NTP exposure. We also assessed the potential of NTP to enhance immunogenicity in these cells and assayed phagocytosis of NTP-exposed leukemic cells by macrophages. Our results highlight the significance of target-mediated modulation of plasma chemical species in the development and clinical use of protocols involving plasma sources for use in cancer therapeutic application. ABSTRACT: Non-thermal plasma application to cancer cells is known to induce oxidative stress, cytotoxicity and indirect immunostimulatory effects on antigen presenting cells (APCs). The purpose of this study was to evaluate the responses of two leukemic cell lines—Jurkat T lymphocytes and THP-1 monocytes—to NTP-generated reactive oxygen and nitrogen species (RONS). Both cell types depleted hydrogen peroxide, but THP-1 cells neutralized it almost immediately. Jurkat cells transiently blunted the frequency-dependent increase in nitrite concentrations in contrast to THP-1 cells, which exhibited no immediate effect. A direct relationship between frequency-dependent cytotoxicity and mitochondrial superoxide was observed only in Jurkat cells. Jurkat cells were very responsive to NTP in their display of calreticulin and heat shock proteins 70 and 90. In contrast, THP-1 cells were minimally responsive or unresponsive. Despite no NTP-dependent decrease in cell surface display of CD47 in either cell line, both cell types induced migration of and phagocytosis by APCs. Our results demonstrate that cells modulate the RONS-mediated changes in liquid chemistry, and, importantly, the resultant immunomodulatory effects of NTP can be independent of NTP-induced cytotoxicity.