Abstract
Because natural killer (NK) cells can be potent anti-tumor effectors after allogeneic stem cell transplantation, we investigated NK reconstitution and receptor expression in patients undergoing allogeneic hematopoietic stem cell transplantation, focusing on the activating receptors that trigger anti-tumor responses. We determined that NK levels in the peri-transplant period were inversely proportional to the dramatic rise and fall in plasma levels of the NK homeostatic cytokine IL-15, which increased more than 50-fold from pretreatment to the day of transplant during the lymphoreductive preparative regimen. Furthermore, in NK cells cultured with IL-15, we observed an up-regulation of the activating receptors NKG2D, NKp30, and NKp46, associated with an increase in anti-tumor lytic activity. Similarly, the expression of these activating receptors increased significantly during the early post-transplant period, concurrent with a rapid increase in total NK cells and a shift toward increased expression of CD56. These data suggest that the cytokine milieu of transplants, in particular elevated levels of IL-15, may contribute to anti-tumor efficacy post-transplant by enhancing the recovery of NK subsets and modulating expression of activating receptors.
MeSH terms
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Adult
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Aged
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CD56 Antigen / biosynthesis
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CD56 Antigen / immunology
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Cells, Cultured
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Female
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Graft vs Leukemia Effect / drug effects
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Graft vs Leukemia Effect / immunology*
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Hematopoietic Stem Cell Transplantation*
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Humans
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Interleukin-15 / blood
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Interleukin-15 / immunology*
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Interleukin-15 / pharmacology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Killer Cells, Natural / pathology
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Lymphocyte Depletion
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Lymphoproliferative Disorders / blood
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Lymphoproliferative Disorders / immunology
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Lymphoproliferative Disorders / pathology
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Lymphoproliferative Disorders / therapy
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Male
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Middle Aged
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Myelodysplastic Syndromes / blood
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Myelodysplastic Syndromes / immunology
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Myelodysplastic Syndromes / pathology
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Myelodysplastic Syndromes / therapy
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NK Cell Lectin-Like Receptor Subfamily K
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Natural Cytotoxicity Triggering Receptor 1
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Natural Cytotoxicity Triggering Receptor 3
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Primary Myelofibrosis / blood
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Primary Myelofibrosis / immunology
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Primary Myelofibrosis / pathology
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Primary Myelofibrosis / therapy
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Receptors, Immunologic / biosynthesis
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Receptors, Immunologic / immunology*
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Receptors, Natural Killer Cell
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Transplantation, Homologous
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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CD56 Antigen
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Interleukin-15
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KLRK1 protein, human
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NCR1 protein, human
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NCR3 protein, human
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NK Cell Lectin-Like Receptor Subfamily K
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Natural Cytotoxicity Triggering Receptor 1
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Natural Cytotoxicity Triggering Receptor 3
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Receptors, Immunologic
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Receptors, Natural Killer Cell