title: CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT.
abstract: We have recently described a specialized subset of human natural killer (NK) cells with a CD56(dim)CD57(+)NKG2C(+) phenotype that expand specifically in response to cytomegalovirus (CMV) reactivation in hematopoietic cell transplant (HCT) recipients and exhibit properties characteristic of adaptive immunity. We hypothesize that these cells mediate relapse protection and improve post-HCT outcomes. In 674 allogeneic HCT recipients, we found that those who reactivated CMV had lower leukemia relapse (26% (17-35%), P=0.05) and superior disease-free survival (DFS) (55% (45-65%) P=0.04) 1 year after reduced intensity conditioning (RIC) compared with CMV seronegative recipients who experienced higher relapse rates (35% (27-43%)) and lower DFS (46% (38-54%)). This protective effect was independent of age and graft-vs-host disease and was not observed in recipients who received myeloablative regimens. Analysis of the reconstituting NK cells demonstrated that CMV reactivation is associated with both higher frequencies and greater absolute numbers of CD56(dim)CD57(+)NKG2C(+) NK cells, particularly after RIC HCT. Furthermore, expansion of these cells at 6 months posttransplant independently trended toward a lower 2-year relapse risk. Together, our data suggest that the protective effect of CMV reactivation on posttransplant relapse is in part driven by adaptive NK cell responses.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: F
authors.initials: F
authors.lastname: Cichocki
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cooley
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Davis
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: DeFor
authors.affiliation: Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Schlums
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Brunstein
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Diamond
authors.affiliation: Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Verneris
authors.affiliation: Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.|Broeglmann Research Laboratory, Clinical Institute, University of Bergen, Bergen, Norway.
authors.forename: Y T
authors.initials: YT
authors.lastname: Bryceson
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D019002:CD56 Antigen / Q000032:analysis*; D018959:CD57 Antigens / Q000032:analysis*; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000502:physiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000032:analysis*; D012008:Recurrence; D014775:Virus Activation
chemical_list: D019002:CD56 Antigen; D018959:CD57 Antigens; C527059:KLRC2 protein, human; C522918:NCAM1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C