Impact of Activating Killer Immunoglobulin-like Receptor Genotype on Outcome of Unrelated Donor–Hematopoietic Cell Transplantation

Giebel, Sebastian; Nowak, Izabela; Wojnar, Jerzy; Markiewicz, Mirosław; Dziaczkowska, Joanna; Wyleżoł, Iwona; Krawczyk-Kuliś, Małgorzata; Bloch, R.; Kuśnierczyk, Piotr; Hołowiecki, Jerzy

doi:10.1016/j.transproceed.2005.11.091

Cited by 34 publications

(34 citation statements)

References 22 publications

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“…41 Although the importance of inhibitory KIRs has been extensively investigated in HLA-mismatched HSCT, the role of activating KIRs has only been studied in a few other HSCT studies. 38,41,[44][45][46] Our study in related HLA-identical HSCT observed that the incidence of relapse decreased when patients received a graft from activating KIR2DS1 and KIR2DS2 positive donors. 44 Furthermore, Giebel et al 46 found that the presence of KIR2DS2 alone in the donor was associated with a high risk of mortality following unrelated HSCT, presumably caused by a higher incidence of GvHD.…”

Section: Cell Surface Expression Of Hla Class I Moleculesmentioning

confidence: 89%

“…38,41,[44][45][46] Our study in related HLA-identical HSCT observed that the incidence of relapse decreased when patients received a graft from activating KIR2DS1 and KIR2DS2 positive donors. 44 Furthermore, Giebel et al 46 found that the presence of KIR2DS2 alone in the donor was associated with a high risk of mortality following unrelated HSCT, presumably caused by a higher incidence of GvHD. Finally, a study published by Gagne et al 45 showed that the risk for GvHD was very high when the KIR genotype of an unrelated donor included activating KIRs that were absent in the recipient KIR genotype.…”

Section: Cell Surface Expression Of Hla Class I Moleculesmentioning

confidence: 89%

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NK cell receptors and their ligands in leukemia

Verheyden

Demanet

2007

Leukemia

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Human natural killer (NK) cells are built to kill abnormal cells but to preserve autologous normal cells. To accomplish this task, they are equipped with a large number of inhibiting and activating receptors. Ligation with corresponding ligands will determine whether the NK cell becomes activated to destroy the abnormal cell. This review will focus on the abnormalities of NK cell receptors and their putative ligands found in patients with leukemia, which can lead to an inadequate function of NK cells allowing these malignant cells to escape from NK cell destruction. In recent years it has become clear that NK cells in the haploidentical hematopoietic stem cell transplantation (HSCT) setting are very effective in eliminating residual acute myeloid, but not acute lymphoid, leukemic cells. In this regard, we also reviewed published studies of retrospective cohorts of HSCT investigating the potential beneficial effect of killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) ligands on NK alloreactivity. Manipulating NK cell inhibition or activation could lead to new forms of immunotherapy, ultimately leading to the elimination of resistant leukemic cells.

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Section: Cell Surface Expression Of Hla Class I Moleculesmentioning

confidence: 89%

Section: Cell Surface Expression Of Hla Class I Moleculesmentioning

confidence: 89%

NK cell receptors and their ligands in leukemia

Verheyden

Demanet

2007

Leukemia

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“…17,18 In addition to the inhibitory KIRs and HLA class I molecules, the potential clinical significance of activating KIRs, for which the ligands and functions are not well identified, 19 is receiving increasing attention. The presence of the KIR2DS2 gene in the donor has been associated with a high risk of mortality following URD-HSCT, 20 whereas the presence of two activating KIRs, 2DS1 and 2DS2, in the donor has been significantly associated with a decreased leukemic relapse rate. 8 Moreover, a recently published study has shown that another activating KIR gene, KIR2DS5, is associated with leukemia-free survival after HSCT in CML patients.…”

Section: Introductionmentioning

confidence: 99%

The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population

Zhao

Lai

et al. 2010

Bone Marrow Transplant

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The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donorrecipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P ¼ 0.019, HR ¼ 0.329), mainly in myeloid disease (P ¼ 0.003, HR ¼ 0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P ¼ 0.034, HR ¼ 0.430) and disease-free survival (DFS) (P ¼ 0.024, HR ¼ 0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P ¼ 0.003, HR ¼ 5.046), decreased OS (P ¼ 0.004, HR ¼ 3.181) and DFS (P ¼ 0.003, HR ¼ 2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.

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“…5 As NK cells are efficient effectors in eradicating tumor cells, they have an important function in the anti-tumor response after allogeneic stem cell transplantation (SCT). [6][7][8][9] In HLA-haploidentical SCT, Ruggeri et al 10 showed that donor alloreactive NK cells isolated from peripheral blood of the recipient were able to lyse tumor cells derived from the recipient, implying that within 1 month after SCT, NK cells may be able to provide some degree of immune reactivity by targeting residual tumor cells still present in the recipient. Indeed, fast recovery of NK cells and predicted alloreactivity toward host tumor cells has been associated with decreased relapse rates and better overall survival of the patient.…”

Section: Introductionmentioning

confidence: 99%

CD3+/CD19+-depleted grafts in HLA-matched allogeneic peripheral blood stem cell transplantation lead to early NK cell cytolytic responses and reduced inhibitory activity of NKG2A

et al. 2009

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Natural killer (NK) cells have an important function in the antitumor response early after stem cell transplantation (SCT). As part of a prospective randomized phase III study, directly comparing the use of CD3 þ /CD19 þ -depleted peripheral blood stem cell (PBSC) harvests with CD34 þ -selected PBSC harvests in allogeneic human leukocyte antigen-matched SCT, we here show that the use of CD3 þ /CD19 þ -depleted PBSC grafts leads to early NK cell repopulation and reconstitution of the CD56 dim and CD56 bright NK cell subsets, with concomitant high cytolytic capacity. In the CD34 group, this process took significantly longer. Moreover, in the CD3/19 group after reconstitution, a higher percentage of killer immunoglobulin-like receptor-positive NK cells was found. Although similar percentages of CD94-positive NK cells were found in both groups, in the CD34 group, almost all expressed the inhibitory CD94:NKG2A complex, whereas in the CD3/19 group, the inhibitory CD94:NKG2A and the activating CD94:NKG2C complex were equally distributed. This preferential development of NKG2C-expressing NK cells in the CD3/19 group was paralleled by a loss of NKG2A-mediated inhibition of NK cell degranulation. These results show that the use of CD3 þ /CD19 þ -depleted grafts facilitates strong NK cell cytolytic responses directly after SCT, and the rapid emergence of an NK cell receptor phenotype that is more prone to activation.

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Impact of Activating Killer Immunoglobulin-like Receptor Genotype on Outcome of Unrelated Donor–Hematopoietic Cell Transplantation

Cited by 34 publications

References 22 publications

NK cell receptors and their ligands in leukemia

NK cell receptors and their ligands in leukemia

The beneficial impact of missing KIR ligands and absence of donor KIR2DS3 gene on outcome following unrelated hematopoietic SCT for myeloid leukemia in the Chinese population

CD3+/CD19+-depleted grafts in HLA-matched allogeneic peripheral blood stem cell transplantation lead to early NK cell cytolytic responses and reduced inhibitory activity of NKG2A

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