Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/37511
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dc.contributor.authorSmallwood, Dawn T.-
dc.contributor.authorApollonio, Benedetta-
dc.contributor.authorWillimott, Shaun-
dc.contributor.authorLezina, Larissa-
dc.contributor.authorAlharthi, Afaf-
dc.contributor.authorAmbrose, Ashley R.-
dc.contributor.authorDe Rossi, Giulia-
dc.contributor.authorRamsay, Alan G.-
dc.contributor.authorWagner, Simon D.-
dc.date.accessioned2016-05-11T14:08:17Z-
dc.date.available2016-05-11T14:08:17Z-
dc.date.issued2016-04-26-
dc.identifier.citationBlood, 2016, 128 (4), pp. 542-552en
dc.identifier.urihttp://www.bloodjournal.org/content/early/2016/04/26/blood-2015-11-682377?sso-checked=trueen
dc.identifier.urihttp://hdl.handle.net/2381/37511-
dc.description.abstractThe complex interplay between cancer cells, stromal cells and immune cells in the tumor microenvironment (TME) regulates tumorigenesis and provides emerging targets for immunotherapies. Crosstalk between CD4(+) T cells and proliferating chronic lymphocytic leukemia (CLL) tumor B cells occurs within lymphoid tissue pseudo-follicles and investigating these interactions is essential to understand both disease pathogenesis and the effects of immunotherapy. Tumor-derived extracellular vesicle (EV) shedding is emerging as an important mode of intercellular communication in the TME. In order to characterize tumor EVs released in response to T cell-derived TME signals, we performed microRNA (miR) profiling of EVs released from CLL cells stimulated with CD40 and IL-4. Our results reveal an enrichment of specific cellular miRNAs including miR-363 within EVs derived from CD40/IL-4 stimulated CLL cells compared to parental cell miRNA content and control EVs from unstimulated CLL cells. We demonstrate that autologous patient CD4(+) T cells internalize CLL-EVs containing miR-363 that targets the immunomodulatory molecule CD69. We further reveal that autologous CD4(+) T cells that are exposed to EVs from CD40/IL-4 stimulated CLL cells exhibit enhanced migration, immunological synapse signaling and interactions with tumor cells. Knockdown of miR-363 in CLL cells prior to CD40/IL-4 stimulation, prevented the ability of CLL-EVs to induce increased synapse signaling and confer altered functional properties to CD4(+) T cells. Taken together, these data reveal a novel role for CLL-EVs in modifying T cell function that highlights unanticipated complexity of intercellular communication that may have implications for bidirectional CD4(+) T-cell:tumor interactions within the TME.en
dc.language.isoenen
dc.publisherAmerican Society of Hematologyen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/27118451-
dc.rightsCopyright © the authors, 2016. This version is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en
dc.titleExtracellular vesicles released by CD40/IL-4 stimulated chronic lymphocytic leukemia cells confer altered functional properties to CD4+ T cellsen
dc.typeJournal Articleen
dc.identifier.doi10.1182/blood-2015-11-682377-
dc.identifier.eissn1528-0020-
dc.identifier.piiblood-2015-11-682377-
dc.description.statusPeer-revieweden
dc.description.versionPost-printen
dc.type.subtypeJOURNAL ARTICLE-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cancer Studies and Molecular Medicineen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Canceren
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Molecular & Cellular Bioscienceen
dc.dateaccepted2016-04-20-
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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