期刊
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
卷 96, 期 9, 页码 1302-1309出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2010.039743
关键词
exosomes; acute myeloid leukemia; acute myeloid leukemia; TGF-beta 1; NK cells; interleukin 15
类别
资金
- NIH [P01 CA109688]
- Polish Ministry of Science and Higher Education [NN401047738]
- Foundation for Polish Science [Homing Plus/2010-1/13]
Background Natural killer cell cytotoxicity is decreased in patients with acute myeloid leukemia in comparison to that in normal controls. Tumor-derived microvesicles present in patients' sera exert detrimental effects on immune cells and may influence tumor progression. Design and Methods We investigated the microvesicle protein level, molecular profile and suppression of natural killer cell activity in patients with newly diagnosed acute myeloid leukemia. Results The patients' sera contained higher levels of microvesicles compared to the levels in controls (P<0.001). Isolated microvesicles had a distinct molecular profile: in addition to conventional microvesicle markers, they contained membrane-associated transforming growth factor-beta 1, MICA/MICB and myeloid blasts markers, CD34, CD33 and CD117. These microvesicles decreased natural killer cell cytotoxicity (P<0.002) and down-regulated expression of NKG2D in normal natural killer cells (P<0.001). Sera from patients with acute myeloid leukemia contained elevated levels of transforming growth factor-beta, and urea-mediated dissociation of microvesicles further increased the levels of this protein. Neutralizing anti-transforming growth factor-beta 1 antibodies inhibited microvesicle-mediated suppression of natural killer cell activity and NKG2D down-regulation. Interleukin-15 protected natural killer cells from adverse effects of tumor-derived microvesicles. Conclusions We provide evidence for the existence in acute myeloid leukemia of a novel mechanism of natural killer cell suppression mediated by tumor-derived microvesicles and for the ability of interleukin-15 to counteract this suppression.
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