Format

Send to

Choose Destination
J Immunol. 2016 Feb 1;196(3):1400-11. doi: 10.4049/jimmunol.1501434. Epub 2016 Jan 8.

Naive Donor NK Cell Repertoires Associated with Less Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation.

Author information

1
Department of Hematology, Karolinska University Hospital, 14186 Stockholm, Sweden; Center for Infectious Medicine, Karolinska Institutet, 14186 Stockholm, Sweden;
2
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway;
3
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway;
4
Center for Infectious Medicine, Karolinska Institutet, 14186 Stockholm, Sweden;
5
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway; Institute of Cancer Genetics and Informatics, Oslo University Hospital, 3010 Oslo, Norway; Department of Informatics, University of Oslo, 0316 Oslo, Norway; and.
6
Department of Hematology, Karolinska University Hospital, 14186 Stockholm, Sweden;
7
Department of Hematology, Karolinska University Hospital, 14186 Stockholm, Sweden; Center for Infectious Medicine, Karolinska Institutet, 14186 Stockholm, Sweden; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, 0310 Oslo, Norway; K.G. Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway kalle.malmberg@ki.se.

Abstract

Acute and latent human CMV cause profound changes in the NK cell repertoire, with expansion and differentiation of educated NK cells expressing self-specific inhibitory killer cell Ig-like receptors. In this study, we addressed whether such CMV-induced imprints on the donor NK cell repertoire influenced the outcome of allogeneic stem cell transplantation. Hierarchical clustering of high-resolution immunophenotyping data covering key NK cell parameters, including frequencies of CD56(bright), NKG2A(+), NKG2C(+), and CD57(+) NK cell subsets, as well as the size of the educated NK cell subset, was linked to clinical outcomes. Clusters defining naive (NKG2A(+)CD57(-)NKG2C(-)) NK cell repertoires in the donor were associated with decreased risk for relapse in recipients with acute myeloid leukemia and myelodysplastic syndrome (hazard ratio [HR], 0.09; 95% confidence interval [CI]: 0.03-0.27; p < 0.001). Furthermore, recipients with naive repertoires at 9-12 mo after hematopoietic stem cell transplantation had increased disease-free survival (HR, 7.2; 95% CI: 1.6-33; p = 0.01) and increased overall survival (HR, 9.3; 95% CI: 1.1-77, p = 0.04). Conversely, patients with a relative increase in differentiated NK cells at 9-12 mo displayed a higher rate of late relapses (HR, 8.41; 95% CI: 6.7-11; p = 0.02), reduced disease-free survival (HR, 0.12; 95% CI: 0.12-0.74; p = 0.02), and reduced overall survival (HR, 0.07; 95% CI: 0.01-0.69; p = 0.02). Thus, our data suggest that naive donor NK cell repertoires are associated with protection against leukemia relapse after allogeneic HSCT.

PMID:
26746188
DOI:
10.4049/jimmunol.1501434
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire Icon for Norwegian BIBSYS system
Loading ...
Support Center