Article

Alloreactive natural killer cells in hematopoietic stem cell transplantation.

Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Australia.
Leukemia research (impact factor: 2.36). 01/2011; 35(1):14-21. DOI:10.1016/j.leukres.2010.07.030 pp.14-21
Source: PubMed

ABSTRACT Allogeneic hematopoietic stem cell transplantation (HSCT) for leukemia can play a major role in reducing the risk of relapse by inducing a graft versus leukemia (GVL) effect. Here, we review the effectiveness of mismatching inhibitory killer-cell-immunoglobulin-like receptors (KIR) on donor natural killer (NK) cells as a mechanism for GVL. We review the range of KIR and the importance of T cell and NK cell content of the graft, together with considerations of the graft source. Further understanding of conditioning and mechanisms to reduce graft versus host disease (GVHD) will improve our ability to manipulate NK cells in HSCT.

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    Article: Natural killer cell mediated missing-self recognition can protect mice from primary chronic myeloid leukemia in vivo.
    Mika Kijima, Noémie Gardiol, Werner Held
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    ABSTRACT: Natural Killer (NK) cells are thought to protect from residual leukemic cells in patients receiving stem cell transplantation. However, multiple retrospective analyses of patient data have yielded conflicting conclusions regarding a putative role of NK cells and the essential NK cell recognition events mediating a protective effect against leukemia. Further, a NK cell mediated protective effect against primary leukemia in vivo has not been shown directly. Here we addressed whether NK cells have the potential to control chronic myeloid leukemia (CML) arising based on the transplantation of BCR-ABL1 oncogene expressing primary bone marrow precursor cells into lethally irradiated recipient mice. These analyses identified missing-self recognition as the only NK cell-mediated recognition strategy, which is able to significantly protect from the development of CML disease in vivo. Our data provide a proof of principle that NK cells can control primary leukemic cells in vivo. Since the presence of NK cells reduced the abundance of leukemia propagating cancer stem cells, the data raise the possibility that NK cell recognition has the potential to cure CML, which may be difficult using small molecule BCR-ABL1 inhibitors. Finally, our findings validate approaches to treat leukemia using antibody-based blockade of self-specific inhibitory MHC class I receptors.
    PLoS ONE 01/2011; 6(11):e27639. · 4.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Allogeneic hematopoietic
 
cell transplantation
 
conditioning
 
considerations
 
donor natural killer
 
graft
 
graft source
 
host disease
 
HSCT
 
KIR
 
leukemia
 
manipulate NK cells
 
mismatching inhibitory killer-cell-immunoglobulin-like receptors
 
NK
 
NK cell content
 
relapse
 
T cell
 

Hollie J Pegram