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CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT

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...

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Autores principales: Cichocki, Frank, Cooley, Sarah, Davis, Zachary, DeFor, Todd E., Schlums, Heinrich, Zhang, Bin, Brunstein, Claudio G., Blazar, Bruce R., Wagner, John, Diamond, Don J., Verneris, Michael R., Bryceson, Yenan T., Weisdorf, Daniel J., Miller, Jeffrey S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740203/
https://www.ncbi.nlm.nih.gov/pubmed/26416461
http://dx.doi.org/10.1038/leu.2015.260
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author Cichocki, Frank
Cooley, Sarah
Davis, Zachary
DeFor, Todd E.
Schlums, Heinrich
Zhang, Bin
Brunstein, Claudio G.
Blazar, Bruce R.
Wagner, John
Diamond, Don J.
Verneris, Michael R.
Bryceson, Yenan T.
Weisdorf, Daniel J.
Miller, Jeffrey S.
author_facet Cichocki, Frank
Cooley, Sarah
Davis, Zachary
DeFor, Todd E.
Schlums, Heinrich
Zhang, Bin
Brunstein, Claudio G.
Blazar, Bruce R.
Wagner, John
Diamond, Don J.
Verneris, Michael R.
Bryceson, Yenan T.
Weisdorf, Daniel J.
Miller, Jeffrey S.
author_sort Cichocki, Frank
collection PubMed
description 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 to 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-versus-host disease (GvHD) and was not observed in recipients who received myeloablative (MA) 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 post-transplant independently trended toward a lower 2-year relapse risk. Together, our data suggest that the protective effect of CMV reactivation on post-transplant relapse is in part driven by adaptive NK cell responses.
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spelling pubmed-47402032016-05-18 CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT Cichocki, Frank Cooley, Sarah Davis, Zachary DeFor, Todd E. Schlums, Heinrich Zhang, Bin Brunstein, Claudio G. Blazar, Bruce R. Wagner, John Diamond, Don J. Verneris, Michael R. Bryceson, Yenan T. Weisdorf, Daniel J. Miller, Jeffrey S. Leukemia Article 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 to 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-versus-host disease (GvHD) and was not observed in recipients who received myeloablative (MA) 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 post-transplant independently trended toward a lower 2-year relapse risk. Together, our data suggest that the protective effect of CMV reactivation on post-transplant relapse is in part driven by adaptive NK cell responses. 2015-09-29 2016-02 /pmc/articles/PMC4740203/ /pubmed/26416461 http://dx.doi.org/10.1038/leu.2015.260 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Cichocki, Frank
Cooley, Sarah
Davis, Zachary
DeFor, Todd E.
Schlums, Heinrich
Zhang, Bin
Brunstein, Claudio G.
Blazar, Bruce R.
Wagner, John
Diamond, Don J.
Verneris, Michael R.
Bryceson, Yenan T.
Weisdorf, Daniel J.
Miller, Jeffrey S.
CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
title CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
title_full CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
title_fullStr CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
title_full_unstemmed CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
title_short CD56(dim)CD57(+)NKG2C(+) NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
title_sort cd56(dim)cd57(+)nkg2c(+) nk cell expansion is associated with reduced leukemia relapse after reduced intensity hct
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740203/
https://www.ncbi.nlm.nih.gov/pubmed/26416461
http://dx.doi.org/10.1038/leu.2015.260
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