Figure 5.

Impact of vemurafenib and cobimetinib treatment of S and R targets on NK cell activation and NK-mediated lysis. Targets were incubated for 20 hours with medium containing DMSO (5 µM) or vemurafenib (5 µM) and cobimetinib (10 nM), washed, detached, and cocultured for 6 hours with IL-2-activated NK cells. Percentages of degranulating CD107a NK cells toward S and R targets treated or not with inhibitors (n=7) (A). Detection of polyfunctional (CD107a and IFNγ) NK cells in response to targets treated with DMSO or inhibitors: IL-2 +IL-12-activated NK cells were cultured for 6 hours with targets treated or not with inhibitors (B). NK cell-mediated lysis of targets treated or not with inhibitors measured by xCELLigence assay. Targets were cultured 20 hours in medium containing DMSO (0.0001%) alone or with vemurafenib (5 µM) and cobimetinib (10 nM). One representative experiment of three (C). Statistical analyses were performed with the Wilcoxon rank test (*p<0.05). DMSO, dimethyl sulfoxide; IFNγ, interferon gamma; IL, interleukin; NK, natural killer.