Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value.

Combined Genotypic and Phenotypic Killer Cell Ig-Like Receptor Analyses Reveal KIR2DL3 Alleles Displaying Unexpected Monoclonal Antibody Reactivity: Identification of the Amino Acid Residues Critical for Staining

“…Therefore, the selection of optimal donors is based, at the molecular level, on the analysis of donor KIR gene profile and of donor and recipient HLA class I typing. Importantly, recent data have demonstrated that, using combinations of different anti-KIR mAb, it is possible to define the size of the alloreactive NK cell subset (14,(36)(37)(38)(39)(40). Our present data indicate that the evaluation of the pool size of alloreactive NK cells in HSCT can only be possible by the use of appropriate mAb combination.…”

“…This occurs when NK cells express iKIRs that don't recognize any of the HLA class I molecules expressed by allogenic target cells (KIR/KIR ligand mismatch) (32). Remarkably, clinical and experimental data from hematopoietic stem cell transplantation (HSCT) revealed that the presence of a KIR/KIR ligand mismatch in the graft versus host direction correlates with a more favorable clinical outcome (33)(34)(35)(36). The presence of alloreactive NK cells can be predicted by the analysis of the donor KIR gene profile and by the HLA class I typing of both donor and recipient.…”

“…The presence of alloreactive NK cells can be predicted by the analysis of the donor KIR gene profile and by the HLA class I typing of both donor and recipient. The actual presence and size of the alloreactive NK subset can be assessed by cytofluorimetric analysis using appropriate combinations of anti-KIR mAb (14,(36)(37)(38)(39)(40). In these experiments, alloreactive NK cells are identified as a subset expressing iKIRs specific for the mismatched KIR ligand but missing all the other iKIRs and NKG2A.…”

Natural killer cell immune escape in acute myeloid leukemia

“…The involvement of inhibitory KIRs in the escape of AML from NK cells was further demonstrated in the haploidentical HSCT setting, where a mismatch between donor KIRs and recipient human leukocyte antigen ligands was shown to reduce the risk of relapse. 30,31 Although these findings were confirmed by some groups, others failed to show any benefit. [32][33][34][35][36][37][38] Results of those studies are discussed in more detail elsewhere by Verheyden and Demanet.…”

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

“…53 Among immune effectors contained in mobilized allograft, NK cells have a key role; they have been recognized to carry strong GVL power without inducing GVHD in T-deplete haploidentical stem cell transplant, and their infusion within the graft provides both anti-leukemic and anti-viral activity in the early posttransplant period. 54 There is evidence of a detrimental effect of G-CSF on their function, which seems to be transient and not to affect late-phase GVL activity. 55 Given the variety of immune cells contained in the apheresis product, many strategies have been developed in order to rationally select graft effectors and provide designed adoptive immunotherapies, especially in the haploidentical stem cell transplant setting.…”