Downregulation of B7-H6 by HDACi leads to reduced NKp30-dependent degranulation by NK cells. Degranulation of NK-92CI cells in (A-B) or primary NK cells activated with IL-2 in (C-D), in a 4-hour coculture at an 1:1 ratio with HeLa (A,C), or SK-Mel-37 cells (B,D) pretreated with the HDACi SAHA or DMSO solvent control is depicted. NK-cell receptors were blocked with the indicated mAbs. The mean (% specific degranulation) of triplicates ± standard deviation from 1 representative experiment with NK-92CI or of 1 NK-cell donor out of 3 is shown. Representative histograms show the surface staining using anti-B7-H6 mAb 1.18, mIgG1 isotype control, NKG2D-FP, or control-FP of the targets after pretreatment. ns, not significant; **P ≤ .01; ***P ≤ .001.