Influence of KIR and NK Cell Reconstitution in the Outcomes of Hematopoietic Stem Cell Transplantation

Natural killer (NK) cells play a significant role in immune tolerance and immune surveillance. Killer immunoglobin-like receptors (KIRs), which recognize human leukocyte antigen (HLA) class I molecules, are particularly important for NK cell functions. Previous studies have suggested that, in the setting of hematopoietic stem cell transplantation (HSCT), alloreactive NK cells from the donor could efficiently eliminate recipient tumor cells and the residual immune cells. Subsequently, several clinical models were established to determine the optimal donors who would exhibit a graft-vs. -leukemia (GVL) effect without developing graft-vs. -host disease (GVHD). In addition, hypotheses about specific beneficial receptor-ligand pairs and KIR genes have been raised and the favorable effects of alloreactive NK cells are being investigated. Moreover, with a deeper understanding of the process of NK cell reconstitution post-HSCT, new factors involved in this process and the defects of previous models have been observed. In this review, we summarize the most relevant literatures about the impact of NK cell alloreactivity on transplant outcomes and the factors affecting NK cell reconstitution.