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Donor NK cell licensing in control of malignancy in hematopoietic stem cell transplant recipients
Author(s) -
Nowak Jacek,
Kościńska Katarzyna,
MikaWitkowska Renata,
RogatkoKoroś Marta,
Mizia Sylwia,
Jaskuła Emilia,
Polak Małgorzata,
MordakDomagała Monika,
Lange Janusz,
Gronkowska Anna,
Jędrzejczak Wiesław Wiktor,
KyrczKrzemień Sławomira,
Markiewicz Mirosław,
DzierżakMietła Monika,
Tomaszewska Agnieszka,
NasiłowskaAdamska 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,
BoguniaKubik Katarzyna,
GraczykPol Elżbieta,
Witkowska Agnieszka,
MaroszRudnicka Anna,
Nestorowicz Klaudia,
Dziopa Joanna,
Szlendak Urszula,
Warzocha Krzysztof,
Lange and Andrzej
Publication year - 2014
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23802
Subject(s) - hematopoietic stem cell transplantation , human leukocyte antigen , malignancy , immunology , transplantation , oncology , medicine , stem cell , cancer research , biology , antigen , genetics
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.Am. J. Hematol. 89:E176–E183, 2014. © 2014 Wiley Periodicals, Inc.