title: Recipient expression of ligands for donor inhibitory KIRs enhances NK-cell function to control leukemic relapse after haploidentical transplantation.
abstract: Natural killer (NK) cells that express self-HLA-specific receptors (where HLA is human leukocyte antigen) are "licensed" and more readily activated than unlicensed cells; therefore, NK-cell licensing could influence the antileukemia effects of NK cells following haploidentical stem cell transplantation (haplo-SCT). In this study, we compared the functionality of reconstituting NK cells, based on CD107α expression and interferon-γsecretion, in a cohort of 29 patients that expressed (n = 8) or lacked (n = 21) class I human leukocyte antigens for donor inhibitory killer cell immunoglobulin-like receptors (KIRs) following T-cell-replete haplo-SCT. We also addressed whether recipient expression of class I ligands for donor inhibitory KIRs could predict relapse occurrence in another cohort of 188 patients. A longitudinal analysis indicated that patients presenting class I for all donor inhibitory KIRs showed more capable functional NK effector cells when tested against class I negative K562 cells and primary leukemic cells within 3 months of transplantation. The lowest 7-year relapse incidence was observed when donor KIRs were ligated by recipient class I (n = 60) compared with donor-host partnerships where donor KIR(+) cells were ligated by donor, but not recipient class I (n = 86, p = 0.026) or KIRs that were ligated by neither donor nor recipient class I (n = 42, p = 0.043). This study suggests that haplo-SCT recipients presenting class I for donor inhibitory KIRs promote NK-cell licensing, leading to decreased relapse rates.
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Zhao
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Lan-Ping
authors.initials: LP
authors.lastname: Xu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Liu
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D007938:Leukemia / Q000276:immunology / Q000473:pathology / Q000628:therapy; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054340:Receptors, KIR / Q000276:immunology*; D012008:Recurrence; D033581:Stem Cell Transplantation
chemical_list: C573415:IFNG protein, human; D052118:Lysosomal-Associated Membrane Protein 1; D054340:Receptors, KIR; D007371:Interferon-gamma
keywords: HSCT; Haploidentica; KIR; Leukemia; NK cells; T-cell replete