title: Donor NK cell licensing in control of malignancy in hematopoietic stem cell transplant recipients.
abstract: Among cancers treated with allogeneic hematopoietic stem-cell transplantation (HSCT), some are sensitive to natural killer (NK) cell reactivity, described as the "missing self" recognition effect. However, this model disregarded the NK cell licensing effect, which highly increases the NK cell reactivity against tumor and is dependent on the coexpression of inhibitory killer cell immunoglobulin-like receptor (iKIR) and its corresponding HLA Class I ligand. We assessed clinical data, HLA and donor iKIR genotyping in 283 patients with myelo- and lymphoproliferative malignancies who underwent HSCT from unrelated donors. We found dramatically reduced overall survival (OS), progression free survival (PFS), and time to progression (TTP) among patients with malignant diseases with the lack of HLA ligand cognate with this iKIR involved in NK cell licensing in corresponding donor (events 83.3% vs. 39.8%, P = 0.0010; 91.6% vs. 47.7%, P = 0.00010; and 30.0% vs. 17.3%, P = 0.013, for OS, PFS, and TTP, respectively). The extremely adverse PFS have withstand the correction when patient group was restricted to HLA mismatched donor-recipient pairs. The incidence of aGvHD was comparable in two groups of patients. In malignant patients after HSCT the missing HLA ligand for iKIR involved in NK cell licensing in corresponding donor ("missing licensing proof") induced extremely adverse survival of the patients due to the progression of malignancy and not to the aGvHD. Avoiding the selection of HSCT donors with the "missing licensing proof" in the malignant patient is strongly advisable.
authors.affiliation: Department of Immunogenetics, Institute of Hematology and Transfusion Medicine, Warsaw.
authors.forename: Jacek
authors.initials: J
authors.lastname: Nowak
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kościńska
authors.forename: Renata
authors.initials: R
authors.lastname: Mika-Witkowska
authors.forename: Marta
authors.initials: M
authors.lastname: Rogatko-Koroś
authors.forename: Sylwia
authors.initials: S
authors.lastname: Mizia
authors.forename: Emilia
authors.initials: E
authors.lastname: Jaskuła
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Polak
authors.forename: Monika
authors.initials: M
authors.lastname: Mordak-Domagała
authors.forename: Janusz
authors.initials: J
authors.lastname: Lange
authors.forename: Anna
authors.initials: A
authors.lastname: Gronkowska
authors.forename: Wiesław Wiktor
authors.initials: WW
authors.lastname: Jędrzejczak
authors.forename: Sławomira
authors.initials: S
authors.lastname: Kyrcz-Krzemień
authors.forename: Mirosław
authors.initials: M
authors.lastname: Markiewicz
authors.forename: Monika
authors.initials: M
authors.lastname: Dzierżak-Mietła
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Tomaszewska
authors.forename: Barbara
authors.initials: B
authors.lastname: Nasiłowska-Adamska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szczepiński
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Hałaburda
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
authors.forename: Lidia
authors.initials: L
authors.lastname: Gil
authors.forename: Anna
authors.initials: A
authors.lastname: Czyż
authors.forename: Jacek
authors.initials: J
authors.lastname: Wachowiak
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Barańska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kowalczyk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Drabko
authors.forename: Jolanta
authors.initials: J
authors.lastname: Goździk
authors.forename: Barbara
authors.initials: B
authors.lastname: Wysoczańska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Graczyk-Pol
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Witkowska
authors.forename: Anna
authors.initials: A
authors.lastname: Marosz-Rudnicka
authors.forename: Klaudia
authors.initials: K
authors.lastname: Nestorowicz
authors.forename: Joanna
authors.initials: J
authors.lastname: Dziopa
authors.forename: Urszula
authors.initials: U
authors.lastname: Szlendak
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: And Andrzej
authors.initials: AA
authors.lastname: Lange
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D046148:Donor Selection / Q000379:methods*; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural; D008297:Male; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D054340:Receptors, KIR / Q000276:immunology; D061349:Unrelated Donors
chemical_list: D015395:Histocompatibility Antigens Class I; D054340:Receptors, KIR