Abstract
BackgroundThe purpose of our study was to examine sensitivity of MM cells and their SC progenitors (which are characterized by negativity for CD138 and active efflux of Hoechst 33342 dye) to natural killer (NK)‐cell mediated cytotoxicity.MethodsNK cells were generated from peripheral blood mononuclear cells of healthy volunteers and co‐cultured with MM (RPMI 8226) cells for 4 hours. NK cell cytotoxicity was assessed by flow cytometry assay. Three different NK/target cell ratios were used. MMSC represented by side population (SP) (negative for Hoechst and CD138) were quantified as percentage of total viable MM cells.ResultsNK cells exhibited significant cytotoxicity against RPMI 8226 cells in all three ratios. Surprisingly, the strongest cytotoxicity was demonstrated when minimal NK/MM ratio (2.5:1) was used. We hypothesize that this phenomenon could be due to NK‐NK cell fratricide. Remarkably, proportion of the overall viable target cell population, represented by MMSC, decreased.ConclusionsMM cells are sensitive to NK‐mediated cytotoxicity. The finding of major importance was potential susceptibility of MMSC to NK‐cell mediated cytotoxicity which could make NK cells additive armamentarium in treating minimal residual disease in patients with MM.
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