Abstract
The immunosuppressive functions of multipotent mesenchymal stromal cells (MSCs) may give cancer cells a survival advantage. This study tests the hypothesis that MSCs protect leukemia cells from immune clearance. Our results demonstrate that MSCs are capable of inhibiting peripheral blood mononuclear cells (PBMNCs) proliferation and their migration toward leukemic cells by the reduction of CCL5 and CXCL12. In addition, we find that MSCs can inhibit the cytolytic functions of NK-cells and CTLs. TGF-β1 secreted by MSCs is responsible for impaired CTLs and NK function by down-modulating surface NKG2D expression. These inhibitory functions of MSCs have negative effects on the CTLs or NK-mediated graft-versus-leukemia (GVL), particularly in the allogeneic hematopoietic stem cells transplantation setting.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Movement
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Cell Proliferation
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Cells, Cultured
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Chemokine CCL5 / biosynthesis
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Chemokine CXCL12 / biosynthesis
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Hematopoietic Stem Cell Transplantation
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Humans
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Immune Evasion
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Leukemia / immunology
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Mesenchymal Stem Cells / immunology*
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NK Cell Lectin-Like Receptor Subfamily K / biosynthesis*
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RNA Interference
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RNA, Small Interfering
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / metabolism*
Substances
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CCL5 protein, human
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CXCL12 protein, human
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Chemokine CCL5
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Chemokine CXCL12
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KLRK1 protein, human
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NK Cell Lectin-Like Receptor Subfamily K
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RNA, Small Interfering
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Transforming Growth Factor beta1