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Title
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Interleukin-15-cultered dendritic cells enhance anti-tumor gamme delta T cell functions through IL-15 secretion
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Author
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Abstract
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| Dendritic cell (DC) vaccination can be an effective post-remission therapy for acute myeloid leukemia (AML). Yet, current DC vaccines do not encompass the ideal stimulatory triggers for innate gamma delta (gamma delta) T cell anti-tumor activity. Promoting type 1 cytotoxic gamma delta T cells in patients with AML is, however, most interesting, considering these unconventional T cells are primed for rapid function and exert meaningful control over AML. In this work, we demonstrate that interleukin (IL)-15 DCs have the capacity to enhance the anti-tumoral functions of gamma delta T cells. IL-15 DCs of healthy donors and of AML patients in remission induce the upregulation of cytotoxicity-associated and co-stimulatory molecules on the gamma delta T cell surface, but not of co-inhibitory molecules, incite gamma delta T cell proliferation and stimulate their interferon-gamma production in the presence of blood cancer cells and phosphoantigens. Moreover, the innate cytotoxic capacity of gamma delta T cells is significantly enhanced upon interaction with IL-15 DCs, both towards leukemic cell lines and allogeneic primary AML blasts. Finally, we address soluble IL-15 secreted by IL-15 DCs as the main mechanism behind the IL-15 DC-mediated gamma delta T cell activation. These results indicate that the application of IL-15-secreting DC subsets could render DC-based anti-cancer vaccines more effective through, among others, the involvement of gamma delta T cells in the anti-leukemic immune response. |
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Language
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English
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Source (journal)
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Frontiers in immunology. - Place of publication unknown
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Publication
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Place of publication unknown
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2018
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ISSN
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1664-3224
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Volume/pages
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9
(2018)
, 12 p.
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Article Reference
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658
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ISI
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000429581700001
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Pubmed ID
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29692776
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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