KIR-KIRL mismatch constellations promote the alloreactivity of cytokine-matured NK cells toward pediatric BCP-ALL in vitro and in vivo. (A) In vitro NK-cell alloreactivity toward BCP-ALL is donor-dependent. Shown is the specific lysis of KIR-KIRL mismatched or matched donors toward the two chosen BCP-ALL samples, P3B relapse and P31G (E:T ratio of 10:1). Cytotoxicity toward K562 cells is included as positive control. Data represent 2 independent experiments performed in triplicates. Donor/patient-specific KIR-KIRL repertoire constellations of the 6 donors SNK9A, SNK10P, SNK21BC, SNK13-15B are depicted in Table 1. (B-C) Donor selection influences the in vivo alloreactivity of NKAES cells toward pediatric BCP-ALL. (B) Experimental setup for Figure 1C. (C) Adoptively transferred NKAES cells of a KIR-KIRL mismatched donor (SNK13B) exert higher in vivo alloreactivity toward P3B than control NKAES cells of a KIR-KIRL matched donor (SNK10P). Data are representative of 1 experiment performed with 11 mice.