(A) Schema of cell stimulation to evaluate functionality and phenotype of cNK cells responding to AFM13 triggering. Clustering channels included for SPADE analysis are shown. B-D) Representative examples of SPADE analysis from 3 different donors showing the expression of KIRs, CD57 and CDK2A/CD94 in the top 2 nodes with highest IFN-γ expression in response to AFM13. Numbers next to each node represent the node ID and color indicates IFN-g median expression. For each donor, selected nodes were backgated to their own viSNE plots to identify their phenotype. (B) IFN-γ production (nodes 1, 8) in this donor was restricted to mature CD57+KIR2DL2/DL3+ NK cells. In this donor, lack of HLA-Bw4 expression in HuT-78 cells correlates with a robust response of KIR3DL1/DS1+ NK cells. (C) The highest IFN-γ production was restricted to terminally matured CD57+KIR2DL2/3+NKG2A- NK cells in this donor. (D) IFN-γ (nodes 2, 3) was produced by both mature and immature NK cells (CD57+NKG2A+CD94+KIR+/−) NK cells in this donor. (E) Median expression of IFN-γ, TNF, MIP1α, CD107a and (F) NK cell markers associated with cell maturation or differentiation in nodes with the highest and lowest IFN-γ median expression per donor. In F, all donors were positive for the depicted KIR. Consolidated data of 10 donors. Bars represent mean ± SEM. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. One-way ANOVA with Tukey pots-hoc test. n=10.