Quantitative HLA Class I Expression and KIR-Mismatch between NK-Cell-Donor and Patient Predict NK Cell Mediated Lysis of Leukemic Cells from Children with Acute Lymphatic Leukemia.

Relapses represent a major problem after transplantations in children with ALL. Natural Killer (NK) cells have been shown to exert remarkable Graft versus Leukemia effects after mismatched stem cell transplantation in myeloic leukemia, whereas the efficacy against lymphatic leukemia is still unclear. We therefore measured intensity of HLA class I expression on leukemic blasts by quantitative FACS analysis and investigated the impact of quantitative HLA class I expression, of several adhesion molecules and of KIR-mismatch on NK cell mediated lysis of the leukemic blasts from 21 pediatric patients with ALL. Expression of HLA class I molecules differed widely from patient to patient (range 5000–500000) and was reduced in comparison to B cells from healthy donors in 70% of cases. NK cells killed leukemic blasts very heterogeneously but a clear association between number of HLA class I molecules per cell and specific lysis (range 13–98%) was found (r²=0.68, p<0.0001). For the subgroup of leukemic blasts without KIR-mismatch, this association was even stronger (r²=0.98), whereas a weak association was found for the subgroup with KIR-mismatch, since most of these targets were lysed more efficiently than one could expect according to HLA class I expression alone. KIR-mismatch alone (t-test, p=0.45) as well as different patterns of adhesion molecules (ICAM1-3, LFA1/3) and CD95 had no significant influence. However, a multivariate model taking both HLA expression and KIR-ligand-mismatch into account, provided an even stronger association (r²=0.87 p<0.0001) for the whole group. Lysis was mainly dependent on HLA class I expression and in addition on KIR-mismatch for these leukemic cells. Assessment of HLA expression on leukemic blasts and KIR-receptor-ligand-mismatch between donor and recipient may be valuable to define patients who will benefit most from a NK mediated GvL effect.