title: Role of Donor Activating KIR-HLA Ligand-Mediated NK Cell Education Status in Control of Malignancy in Hematopoietic Cell Transplant Recipients.
abstract: Some cancers treated with allogeneic hematopoietic stem cell transplantation (HSCT) are sensitive to natural killer cell (NK) reactivity. NK function depends on activating and inhibitory receptors and is modified by NK education/licensing effect and mediated by coexpression of inhibitory killer-cell immunoglobulin-like receptor (KIR) and its corresponding HLA I ligand. We assessed activating KIR (aKIR)-based HLA I-dependent education capacity in donor NKs in 285 patients with hematological malignancies after HSCT from unrelated donors. We found significantly adverse progression-free survival (PFS) and time to progression (TTP) in patients who received transplant from donors with NKs educated by C1:KIR2DS2/3, C2:KIR2DS1, or Bw4:KIR3DS1 pairs (for PFS: hazard ratio [HR], 1.70; P = .0020, Pcorr = .0039; HR, 1.54; P = .020, Pcorr = .039; HR, 1.51; P = .020, Pcorr = .040; and for TTP: HR, 1.82; P = .049, Pcorr = .096; HR, 1.72; P = .096, Pcorr = .18; and HR, 1.65; P = .11, Pcorr = .20, respectively). Reduced PFS and TTP were significantly dependent on the number of aKIR-based education systems in donors (HR, 1.36; P = .00031, Pcorr = .00062; and HR, 1.43; P = .019, Pcorr = .038). Furthermore, the PFS and TTP were strongly adverse in patients with missing HLA ligand cognate with educating aKIR-HLA pair in donor (HR, 3.25; P = .00022, Pcorr = .00045; and HR, 3.82; P = .027, Pcorr = .054). Together, these data suggest important qualitative and quantitative role of donor NK education via aKIR-cognate HLA ligand pairs in the outcome of HSCT. Avoiding the selection of transplant donors with high numbers of aKIR-HLA-based education systems, especially for recipients with missing cognate ligand, is advisable.
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland. Electronic address: jnowak@ihit.waw.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Nowak
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kościńska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Mika-Witkowska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Rogatko-Koroś
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Mizia
authors.affiliation: Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Jaskuła
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Polak
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Mordak-Domagała
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Lange
authors.affiliation: Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gronkowska
authors.affiliation: Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Wiesław Wiktor
authors.initials: WW
authors.lastname: Jędrzejczak
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Sławomira
authors.initials: S
authors.lastname: Kyrcz-Krzemień
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Markiewicz
authors.affiliation: Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Dzierżak-Mietła
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Tomaszewska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nasiłowska-Adamska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szczepiński
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Hałaburda
authors.affiliation: Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.affiliation: Chair and Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Czyż
authors.affiliation: Chair and Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Gil
authors.affiliation: Chair and Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
authors.affiliation: Department of Pediatrics Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Wachowiak
authors.affiliation: Department of Pediatrics Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Barańska
authors.affiliation: Department of Pediatric Hematology, Oncology and Transplantology, Medical University, Lublin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kowalczyk
authors.affiliation: Department of Pediatric Hematology, Oncology and Transplantology, Medical University, Lublin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Drabko
authors.affiliation: Chair of Clinical Immunology and Transplantation Polish-American Institute of Pediatrics, Department of Transplantation Children's University Hospital, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Goździk
authors.affiliation: Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wysoczańska
authors.affiliation: Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Graczyk-Pol
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Witkowska
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Marosz-Rudnicka
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Nestorowicz
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Dziopa
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Szlendak
authors.affiliation: Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.affiliation: Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Poland; Department of Clinical Immunology, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D005260:Female; D020350:Graft vs Tumor Effect / Q000235:genetics / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology*; D061349:Unrelated Donors
chemical_list: D015395:Histocompatibility Antigens Class I; D054340:Receptors, KIR
keywords: Activating killer cell immunoglobulin-like receptors; Bone marrow donor selection; Hematopoietic stem cell transplantation; Malignant diseases; Missing ligand; Natural killer cell education