Donor NK cell licensing in control of malignancy in hematopoietic stem cell transplant recipients

Nowak, Jacek; Kościńska, Katarzyna; Mika‐Witkowska, Renata; Rogatko-Koroś, Marta; Mizia, Sylwia; Jaskuła, Emilia; Polak, Małgorzata; Mordak‐Domagała, Monika; Lange, Janusz; Gronkowska, Anna; Jędrzejczak, Wiesław Wiktor; Kyrcz‐Krzemień, Sławomira; Markiewicz, Mirosław; Dzierżak‐Mietła, Monika; Tomaszewska, Agnieszka; Nasiłowska-Adamska, Barbara; Szczepiński, Andrzej; Hałaburda, Kazimierz; Hellmann, Andrzej; Komarnicki, Mieczysław; Gil, Lidia; Czyż, Anna; Wachowiak, Jacek; Barańska, Małgorzata; Kowalczyk, Jerzy; Drabko, Katarzyna; Goździk, Jolanta; Wysoczańska, Barbara; Bogunia‐Kubik, Katarzyna; Graczyk‐Pol, Elżbieta; Witkowska, Agnieszka; Marosz-Rudnicka, Anna; Nestorowicz, Klaudia; Dziopa, Joanna; Szlendak, Urszula; Warzocha, Krzysztof; Lange, A.

doi:10.1002/ajh.23802

Cited by 23 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a mouse model, Yokoyama and Kim (2006) demonstrated that NK cells are regulated by the host class I MHC molecules. Nowak et al (2014) also revealed dramatic reductions in overall survival, progression-free survival and time to progression among patients with malignant disease lacking cognate HLA ligands for donor inhibitory KIRs involved in NK cell licensing following unrelated transplantation, further confirming the key roles of class I ligands for donor inhibitory KIRs in recipients in NK cell licensing post-transplantation. Boudreau et al (2016) recently demonstrated that NK cell reactivity increased or decreased when HLA was acquired from neighbouring cells or was silenced in educated cells, respectively.…”

Section: Discussionmentioning

confidence: 67%

“…In the setting of CBT, Sekine et al (2016) reported that HLA-C1/x patients should receive an HLA-C1-KIR2DL2/L3/S2 cord blood graft, while HLA-C2/C2 patients may benefit from an HLA-C2-KIR2DL1/S1 graft. Nowak et al (2014) also revealed dramatic reductions in overall survival, progression-free survival and time to progression among patients with malignant disease lacking cognate HLA ligands for donor inhibitory KIRs involved in NK cell licensing following unrelated transplantation, further confirming the key roles of class I ligands for donor inhibitory KIRs in recipients in NK cell licensing post-transplantation. In accordance with their report, our findings have indicated that HLA-C1/C1 patients should receive an HLA-C1C1 haplograft, while HLA-C1C2 patients should receive an HLA-C1C2 haplo-graft; in addition, HLA-Bw4/X patients should receive an HLA-Bw4X haplo-graft post haplo-SCT.…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

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

Zhao

Luo

et al. 2017

Br J Haematol

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 67%

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

Zhao

Luo

et al. 2017

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…The binding of HLA to a cognate inhibitory KIR has a dual inhibitory and educational function (Kim et al, ; Long et al, ). While NK cell activation may be the result of negative recognition (missing ligand recognition) by inhibitory KIRs, NK cell education or licensing depends on the positive binding of KIR to cognate HLA and hence “arming” NK cells (Kim et al, ; Nowak et al, ). To become licensed, NK cells distinguish between cognate and nonbinding HLAs using KIR.…”

Section: Selection Of Hla Class I Motifs Involved In Kir Bindingmentioning

confidence: 99%

“…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%

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Lack of donor HLA ligand for cognate inhibitory KIR has been associated with adverse survival due to disease progression after URD HCT 20 .…”

Section: Introductionmentioning

confidence: 99%

Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation

Sobecks

Wang

Askar

et al. 2015

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Natural killer (NK) cells are regulated killer immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of NK reactivity have been associated with improved outcomes following myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n=612) lacking ≥1 KIR ligands experienced higher grade III–IV acute graft-vs.-host disease (GvHD) (HR 1.6, 95%CI 1.16–2.28, p=0.005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II–IV (HR 1.4, p=0.002) and III–IV acute GvHD (HR 1.5, p=0.01) compared to HLA-C2+patients. AML patients with KIR2DS1+, HLA-C2 homozygous donors had greater treatment-related mortality compared to others (HR 2.4, 95%CI 1.4–4.2, p=0.002), but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor activating KIRs or centromeric KIR content, nor for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n=297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.

show abstract

Donor NK cell licensing in control of malignancy in hematopoietic stem cell transplant recipients

Cited by 23 publications

References 31 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

Impact of KIR and HLA Genotypes on Outcomes after Reduced-Intensity Conditioning Hematopoietic Cell Transplantation

Contact Info

Product

Resources

About