文章基本信息

标题：Circulating exosomes carrying an immunosuppressive cargo interfere with cellular immunotherapy in acute myeloid leukemia
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作者：Chang-Sook Hong ; Priyanka Sharma ; Saigopalakrishna S. Yerneni 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-14661-w
语种：English
出版社：Springer Nature
摘要：Exosomes, small (30-150 nm) extracellular vesicles (EVs) isolated from plasma of patients with acute myeloid leukemia (AML) carry leukemia-associated antigens and multiple inhibitory molecules. Circulating exosomes can deliver suppressive cargos to immune recipient cells, inhibiting anti-tumor activities. Pre-therapy plasma of refractory/relapsed AML patients contains elevated levels of immunosuppressive exosomes which interfere with anti-leukemia functions of activated immune cells. We show that exosomes isolated from pre-therapy plasma of the AML patients receiving adoptive NK-92 cell therapy block anti-leukemia cytotoxicity of NK-92 cells and other NK-92 cell functions. NK-92 cells do not internalize AML exosomes. Instead, signaling via surface receptors expressed on NK-92 cells, AML exosomes simultaneously deliver multiple inhibitory ligands to the cognate receptors. The signals are processed downstream and activate multiple suppressive pathways in NK-92 cells. AML exosomes reprogram NK-92 cells, interfering with their anti-leukemia functions and reducing the therapeutic potential of adoptive cell transfers. Plasma-derived exosomes interfere with immune cells used for adoptive cell therapy and may limit expected therapeutic benefits of adoptive cell therapy.