Inhibitory effects of ATRA on DARA-mediated NK cell cytotoxicity. (A-B) Cytotoxicity and DARA-mediated ADCC activity of paired CD38^WT and CD38^KO NK cells against myeloma cell lines pretreated with 50 nM ATRA for 48 hours (mean ± SD). (C) Left panel shows representative FACS analyses data for CD38 expression on NK cells (CD3^–CD56⁺) from patients during ATRA treatment or no therapy. Frozen PB mononuclear cells were thawed and analyzed at once. Right panel shows fold increase of MFI (CD38) of NK cells during ATRA therapy compared with no therapy for 3 different patients. (D) Representative FACS analyses data of CD38 expression on CD38^WT and CD38^KO NK cells 48 hours after incubation with 50 nM ATRA or solvent control. Control and ATRA-treated samples are shown with steel blue and red lines, respectively. Unstained controls are depicted with filled histograms. (E) Viability of CD38^WT and CD38^KO NK cells treated with DARA for 48 hours in the presence of 50 nM ATRA or solvent control compared with that of control samples (mean ± SD). (F-G) Cytotoxicity and DARA-mediated ADCC activity of paired CD38^WT and CD38^KO NK cells against myeloma cell lines in a 48-hour cytotoxicity assay in the presence of 50 nM ATRA or solvent control. E:T ratio is 0.25:1 for MM.1S and 0.5:1 for KMS-11 (mean ± SD).