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

Abstract

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.

Immune Reconstitution after Haploidentical Donor and Umbilical Cord Blood Allogeneic Hematopoietic Cell Transplantation

“…An ongoing prospective, multicenter trial is evaluating the utility of incorporating donor KIR type in selection of allogeneic HCT donors for patients with acute myeloid leukemia (NCT02450708). Further, the ability of tumor cells to down regulate HLA class I creates a mechanism by which NK cells can differentiate between tumor and healthy host tissue, thus leading to activation and tumor killing [ 65 , 66 , 67 ].…”

Non‐KIR NK cell receptors: Role in transplantation of allogeneic haematopoietic stem cells

“…Killer‐cell immunoglobulin‐like receptors (KIRs) are principal members of this group, even though some of them also have activating properties. KIRs are a group of highly polymorphic molecules that recognize specific HLA‐A, HLA‐B and HLA‐C allotypes (Falco et al., 2019; Gao et al., 2020; Partanen et al., 2020; Thielens et al., 2012).…”

“…NK cell activation may be triggered during inflammation, for example following upregulation of stress ligands binding to activating receptors. It may also be triggered by loss of HLA class I expression, which is a hallmark of malignant lotypes (Falco et al, 2019;Gao et al, 2020;Partanen et al, 2020;Thielens et al, 2012).…”

Decreased iKIR-HLA C Pair Confers Worse Clinical Outcomes for Patients With Myeloid Disease Receiving Antithymocyte Globulin-Based Haploidentical Hematopoietic Stem Cell Transplantation

“…Following these observations, numerous clinical studies have explored the impact of KIR on transplant outcomes. However, a large variability was found in these results and several factors may be responsible for these discrepancies, including disease type, transplant regimen, donor-recipient relationship, graft source and graft composition, etc ( 10 – 12 ).…”