CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT
F Cichocki1, S Cooley1, Z Davis1
1Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Insights
Cytomegalovirus (CMV) reactivation in hematopoietic cell transplant (HCT) recipients is linked to reduced leukemia relapse. This effect is associated with an expansion of adaptive natural killer (NK) cells, particularly after reduced intensity conditioning (RIC).
Area of Science:
- Immunology
- Transplantation
- Oncology
Background:
- A specialized subset of human natural killer (NK) cells (CD56dimCD57+NKG2C+) expands in response to cytomegalovirus (CMV) reactivation post-hematopoietic cell transplant (HCT).
- These adaptive-like NK cells are hypothesized to improve outcomes and protect against relapse after HCT.
Purpose of the Study:
- To investigate the association between CMV reactivation and post-transplant relapse rates in allogeneic HCT recipients.
- To determine the role of adaptive NK cell expansion in mediating protection against leukemia relapse.
Main Methods:
- Retrospective analysis of 674 allogeneic HCT recipients.
- Quantification of CD56dimCD57+NKG2C+ NK cell frequencies and numbers post-HCT.
- Correlation of CMV reactivation and NK cell subset expansion with leukemia relapse and disease-free survival (DFS).
Main Results:
- CMV reactivation was associated with significantly lower leukemia relapse rates (26% vs. 35%) and superior DFS (55% vs. 46%) at 1 year post-reduced intensity conditioning (RIC) HCT.
- Higher frequencies and absolute numbers of CD56dimCD57+NKG2C+ NK cells were observed in CMV-reactivating recipients, especially after RIC HCT.
- Expansion of these adaptive NK cells at 6 months post-transplant trended toward a lower 2-year relapse risk.
Conclusions:
- CMV reactivation confers a protective effect against leukemia relapse in allogeneic HCT recipients, particularly those undergoing RIC.
- The expansion of adaptive NK cells (CD56dimCD57+NKG2C+) in response to CMV likely contributes to this relapse protection.
- These findings highlight the potential of leveraging adaptive NK cell responses to improve HCT outcomes.
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.
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