Enhancers and inhibitors of NK-cell cytotoxicity in K562 CML cells and primary CML sample. (A) Top 15 drugs most potently enhancing NK-cell cytotoxicity ordered by the dDSS). (B) Top 15 drugs most potently inhibiting NK-cell cytotoxicity, ordered by the dDSS. (C) Top 15 drugs most potently inhibiting NK-cell viability. (D) Dose-response curves showing the effects of the 3 SMAC mimetics included in the drug library on NK-cell viability. (E) Heat map showing the variability of drug responses across 3 healthy NK-cell donors from a validation drug screen. Red boxes represent enhancement of NK-cell cytotoxicity, whereas purple represents inhibition of NK-cell cytotoxicity. (F) Dose-response curves for the top drugs when validated in 3 different NK-cell donors. Orange curve and points indicate drug responses with coculture of NK cells and target cells, and the blue curve and points indicate drug responses with the target cells only. Curves are drawn using the median percent inhibition values across NK-cell donors shown as darker orange dots, with lighter orange dots indicate individual NK-cell donor percent inhibition values. BTK, Bruton tyrosine kinase; CDK, cyclin-dependant kinase; CSC, cancer stem cell; ERK, extracellular signal-regulated kinase; HDAC, histone deacetylase inhibitor; HER, human epidermal growth factor receptor; IMPDH, inosine-5'-monophosphate dehydrogenase; VDAC, voltage dependant anion channel.