High-throughput drug screen identifies drugs modulating NK-cell cytotoxicity. (A) Schematic of the high-throughput coculture DSRT. (B) K562-luc cell viability with different E:T ratios of NK cells cocultured for 4 hours or 24 hours, in which bars indicate standard deviations and dots indicate the 6 technical replicates for each condition. (C) Overview of the main drug classes included in the compound library. Individual drugs are found in supplemental Table 1. (D) Overview of the landscape of drug responses in the 24-hour NK-cell cytotoxicity screen. A positive dDSS between NK-cell–treated and control drug screens indicates that the drug enhances NK-cell cytotoxicity, whereas a negative score indicates inhibition. The dotted line indicates cutoff values of 7.5 and −7.5. Drugs falling between the dotted lines are considered either only modestly effective or have no effect, whereas drugs falling outside the dotted lines are considered to have an effect.