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 (γδ) 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 γδ 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 γδ T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs.
Van Acker, H., Beretta, O., Anguille, S., Caluwé, L., Papagna, A., Van den Bergh, J., et al. (2017). Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells. ONCOTARGET, 8(8), 13652-13665 [10.18632/oncotarget.14622].
|Citazione:||Van Acker, H., Beretta, O., Anguille, S., Caluwé, L., Papagna, A., Van den Bergh, J., et al. (2017). Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells. ONCOTARGET, 8(8), 13652-13665 [10.18632/oncotarget.14622].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells|
|Autori:||Van Acker, H; Beretta, O; Anguille, S; Caluwé, L; Papagna, A; Van den Bergh, J; Willemen, Y; Goossens, H; Berneman, Z; Van Tendeloo, V; Smits, E; Foti, M; Lion, E|
|Data di pubblicazione:||2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.18632/oncotarget.14622|
|Appare nelle tipologie:||01 - Articolo su rivista|