Recipient expression of ligands for donor inhibitory KIRs enhances NK‐cell function to control leukemic relapse after haploidentical transplantation

Zhao, Xiang‐Yu; Chang, Ying‐Jun; Zhao, Xinyang; Xu, Lei; Zhang, Xiao-Hui; Liu, Kai-Yan; Li, Dan; Huang, Xiao‐Jun

doi:10.1002/eji.201445057

Cited by 37 publications

(27 citation statements)

References 43 publications

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“…Our previous studies demonstrated that NK cell licensing is promoted in unmanipulated haploidentical SCT (haplo-SCT) recipients presenting class I ligands for donor inhibitory KIRs, leading to a decreased relapse rate Zhao et al, 2007Zhao et al, , 2014Zhao et al, , 2015. Further, Sekine et al (2016) demonstrated that cord blood (CB) selection based on the combination of NK cell licensing and activation of KIRs may improve patient outcome after CB transplantation (CBT).…”

Section: Discussionmentioning

confidence: 99%

“…Our previously published data have demonstrated that recipient expression of ligands for donor inhibitory KIRs enhances NK cell function to control leukaemic relapse after haploidentical transplantation (Zhao et al, 2014(Zhao et al, , 2015. On this basis, we further demonstrated that CMV reactivation was reduced when donor KIRs were ligated by recipient and donor class I at the same time, when compared with donorhost partnerships in which donor KIRs were ligated by donor but not recipient class I or were ligated by recipient but not donor class I or KIRs that were ligated by neither donor nor recipient class I.…”

Section: Discussionmentioning

confidence: 99%

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Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

Zhao

Luo

et al. 2017

Br J Haematol

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Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation. Donor-recipient KIR ligand matching decreased CMV reactivation [51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012], refractory CMV infection [17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004] and CMV disease [3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024] by day 100 post-transplantation. In addition, the percentage of γ-interferon expression on donor-derived NK cells was significantly higher in the recipients among the recipient-donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft-versus-host or host-versus-graft direction mismatch on days 30 and 100 post-transplantation (P = 0·036 and 0·047, respectively). These findings have suggested that donor-recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell-mediated protection against CMV reactivation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

Zhao

Luo

et al. 2017

Br J Haematol

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“…Within the frames of recognition, HLA class I molecules are evolutionally and functionally selected in close correlation with the specificity of the KIR genes (Guinan et al, ; Parham, ; Parham, Norman, Abi‐Rached, & Guethlein, ). In HSC transplant patients, increasing evidence shows that unlike KIR ligand mismatch the cognate HLA:KIR pairings are of primary clinical importance for cancer immunosurveillance, lower relapse incidence and better survival (Gaafar et al, ; Graczyk‐Pol et al, ; Hoseinian et al, ; Nowak et al, , ; Rogatko‐Koroś et al, ; Zhao et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Due to recombination, mutation and adaptive introgression events, numerous HLA molecular polymorphic interfaces are evolutionally selected to encounter specific KIR molecules (Abi‐Rached et al, ; Foley et al, ; Parham & Moffett, ; Pende et al, ; Winter, Gumperz, Parham, Long, & Wagtmann, ). These HLA motifs in malignant patients are crucial for the prediction of HLA:KIR cognate pairs and NK cell function including anti‐leukaemic capacity (Pende et al, ; Rogatko‐Koroś et al, ; Zhao et al, ). Of importance, in HLA molecular interfaces, atypical amino acid combinations and exceptions are possible (De Santis et al, ), leading to cognate HLA:KIR pair misassignments and potential blurry clinical results.…”

Section: Introductionmentioning

confidence: 99%

KIR specificity and avidity of standard and unusual C1, C2, Bw4, Bw6 and A3/11 amino acid motifs at entire HLA:KIR interface between NK and target cells, the functional and evolutionary classification of HLA class I molecules

Gwozdowicz

Nestorowicz

Graczyk‐Pol

et al. 2019

Int J Immunogenetics

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Natural killer (NK) cells make vital contributions to the immune system and the reproductive system. Notably, NK cells of donor origin can recognize and kill residual leukaemic cells and cure malignant patients in hematopoietic stem cell (HSC) transplant setting. NK cell function is regulated by KIRs that recognize cognate HLA class I molecules on target cells, depending on their amino acid residues. In review, we addressed the question of binding capacity and avidity of HLA class I molecules to different killer cell immunoglobulin‐like receptors (KIRs) depending on all interacting amino acid residues both on HLA and KIR side. We searched PubMed database and analysed available HLA:KIR crystallographic data for amino acid residues in HLA molecules, those physically involved in binding KIRs (termed here the “entire KIR interface”). Within entire KIR interface, we selected five functional sequence motifs (14–19, 66–76, 77–84, 88–92 and 142–151) and classified them according to the conservation of their amino acid sequences among 8,942 HLA class I molecules. Although some conserved amino acid motifs were shared by different groups of KIR ligands, the HLA motif combinations were exclusive for the ligand groups. In 135 common HLA class I molecules with known HLA:KIR recognition, we found 54 combinations of five motifs in each of the KIR‐binding interfaces (C1, C2, Bw4, A3/11) and conserved non‐KIR‐binding interfaces. Based on the entire KIR interface, this analysis allowed to classify 8,942 HLA class I molecules into KIR specificity groups. This functional and evolutionary classification of entire KIR interfaces provides a tool for unambiguously predicting HLA:KIR interactions for common and those HLA molecules that have not yet been functionally tested. Considering the entire KIR interface in HLA class I molecules, functional interactions of HLA and KIR can be predicted in immune responses, reproduction and allotransplantation. Further functional studies are needed on the HLA:KIR interaction variations caused by the repertoires of peptides presented by HLA molecules and KIR polymorphisms at allelic level.

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“…Additionally, donor-specific anti-HLA antibodies (DSAs) were indicated to be associated with primary graft failure (GF), transplant-related mortality and inferior overall survival following haplo-HSCT [83]. Donor selection based on other non-HLA systems, such as donor inhibitory killer cell immunoglobulin-like receptors (KIRs), remain to be further elucidated [84].…”

Section: Haploidentical Hematopoietic Stem Cell Transplantation (Haplmentioning

confidence: 99%

Fighting against hematological malignancy in China: from unique system to global impact

Huang

2015

Sci. China Life Sci.

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During recent decades, substantial progress has been made in clinical strategies for treating hematological malignancies. Not only did China benefit from the global progression in the management of acute promyelocytic leukemia, risk-stratification-directed strategies for acute or chronic leukemia and haploidentical hematopoietic stem cell transplantation, the unique system developed by Chinese doctors has also become inspiration for refining global clinical practice. The multicenter trials and collaborations adhering to international standards might further strengthen the global impact and lead the way in specific fields of research worldwide.

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Recipient expression of ligands for donor inhibitory KIRs enhances NK‐cell function to control leukemic relapse after haploidentical transplantation

Abstract: Keywords: KIR r Haploidentica r HSCT r NK cells r T-cell replete r Leukemia Additional supporting information may be found in the online version of this article at the publisher's web-site

Cited by 37 publications

References 43 publications

Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

Recipient‐donor KIR ligand matching prevents CMV reactivation post‐haploidentical T cell‐replete transplantation

KIR specificity and avidity of standard and unusual C1, C2, Bw4, Bw6 and A3/11 amino acid motifs at entire HLA:KIR interface between NK and target cells, the functional and evolutionary classification of HLA class I molecules

Fighting against hematological malignancy in China: from unique system to global impact

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