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Stem cell transplantation

CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT

Leukemia volume 30, pages 456–463 (2016)Cite this article

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Abstract

We have recently described a specialized subset of human natural killer (NK) cells with a CD56dimCD57+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 CD56dimCD57+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.

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Acknowledgements

We thank the following shared resources within the Masonic Cancer Center at the University of Minnesota: The Translational Therapy Laboratory, Flow Cytometry Shared Resource, Clinical Trials Office, Oncology Medical Informatics and Services, and the Biostatistical Core. This work was supported by NIH P30 CA77598, R01 CA72669 (to BRB), 1R01 CA181045 (to DJD), 5R01 CA077544 (to DJD) and P30 CA033572 (City of Hope Cancer Center). FC is an Amy Strelzer Manasevit Research Program Scholar and is supported by a National Marrow Donor Program Award (CON000000052310).

Author contributions

FC and SC contributed to the study design, analyzed and interpreted data and wrote the manuscript. ZD analyzed data. TED performed the biostatistical analyses for the study. HS contributed to the conception of the study. BZ performed NK cell function assays. CGB, BRB, JS and MRV contributed to the study design and sample procurement. DJD reviewed and edited the manuscript. YTB contributed to the conception of the study and interpretation of results. DJW and JSM contributed to the study design and sample procurement, analyzed and interpreted data and wrote the manuscript.

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Authors and Affiliations

  1. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    F Cichocki, S Cooley, Z Davis, B Zhang, C G Brunstein, D J Weisdorf & J S Miller

  2. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    T E DeFor, B R Blazar & J Wagner

  3. Department of Medicine, Centre for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    H Schlums & Y T Bryceson

  4. Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA

    D J Diamond

  5. Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    M R Verneris

  6. Broeglmann Research Laboratory, Clinical Institute, University of Bergen, Bergen, Norway

    Y T Bryceson

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  1. F Cichocki
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Correspondence to J S Miller.

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Cichocki, F., Cooley, S., Davis, Z. et al. CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT. Leukemia 30, 456–463 (2016). https://doi.org/10.1038/leu.2015.260

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