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Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells

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dc.contributor.author Van Acker, H. H. en_US
dc.contributor.author Beretta, O. en_US
dc.contributor.author Anguille, S. en_US
dc.contributor.author De Caluwé, L. en_US
dc.contributor.author Papagna, A. en_US
dc.contributor.author Van den Bergh, J. M. en_US
dc.contributor.author Willemen, Y. en_US
dc.contributor.author Goossens, H. en_US
dc.contributor.author Berneman, Z. N. en_US
dc.contributor.author Van Tendeloo, V. F. en_US
dc.contributor.author Smits, E. L. en_US
dc.contributor.author Foti, M. en_US
dc.contributor.author Lion, E. en_US
dc.date.accessioned 2019-06-04T12:22:43Z
dc.date.available 2019-06-04T12:22:43Z
dc.date.issued 2017 en_US
dc.identifier.issn 1949-2553 en_US
dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.14622 en_US
dc.identifier.other http://lib.itg.be/pdf/itg/2017/2017onco13652.pdf en_US
dc.identifier.other 78 en_US
dc.identifier.other ITG-B4B; DBM; U-VIROL; JIF; DOI; PDF; Abstract; ITMPUB; DSPACE65 en_US
dc.identifier.uri http://hdl.handle.net/10390/10821
dc.description.abstract Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells. Here, we demonstrate that IL-4 DCs are suboptimal in attracting effector lymphocytes, while IL15 DCs provide a favorable chemokine milieu for recruiting CD8+ T cells, natural killer (NK) cells and gamma delta (gammadelta) T cells. Gene expression analysis revealed that IL-15 DCs exhibit a high expression of chemokines involved in antitumor immune effector cell attraction, while IL-4 DCs display a more immunoregulatory profile characterized by the expression of Th2 and regulatory T cell-attracting chemokines. This is confirmed by functional data indicating an enhanced recruitment of granzyme B+ effector lymphocytes by IL-15 DCs, as compared to IL-4 DCs, and subsequent superior killing of tumor cells by the migrated lymphocytes. Elevated CCL4 gene expression in IL-15 DCs and lowered CCR5 expression on both migrated gammadelta T cells and NK cells, led to validation of increased CCL4 secretion by IL15 DCs. Moreover, neutralization of CCR5 prior to migration resulted in an important inhibition of gammadelta T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs. en_US
dc.language English en_US
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/28099143 en_US
dc.subject Immunology en_US
dc.subject Immunotherapy en_US
dc.subject Dendritic cells en_US
dc.title Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells en_US
dc.type Article en_US
dc.citation.issue 8 en_US
dc.citation.jtitle Oncotarget en_US
dc.citation.volume 8 en_US
dc.citation.pages 13652-13665 en_US
dc.citation.abbreviation Oncotarget en_US


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