Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells

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Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells

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Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells

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Título: Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells
Autor: Mendoza Naranjo, Ariadna; Sáez, Pablo J.; Johansson, C. Christian; Ramírez, Marcos; Mandakovic, Dinka; Pereda, Cristian; López, Mercedes N.; Kiessling, Rolf; Sáez, Juan C.; Salazar Onfray, Flavio
Resumen: Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma cell lysate (MCL) and stimulated with TNF-ce (MCL/TNF) acquire a mature phenotype in vitro and are able to trigger tumor-specific immune responses when they are used in melanoma immunotherapy in patients. In this study, we describe that MCL/TNF induces gap junction (GJ)-mediated intercellular communications and promotes melanoma Ag transfer between ex vivo produced hDCs from melanoma patients. hDCs also exhibit increased expression of the GJ-related protein connexin 43, which contributes to GJ plaque formation after MCL/TNF stimulation. The addition of GJ inhibitors suppresses intercellular tumor Ag transfer between hDCs, thus reducing melanoma-specific T cell activation. In summary, we demonstrate that MCL/TNF-stimulated hDCs can establish functional GJ channels that participate in melanoma Ag transfer, facilitating Ag cross-presentation and an effective dendritic cell-mediated melanoma-specific T cell response. These results suggest that GJs formed between hDCs used in cancer vaccination protocols could be essentials for the establishment of a more efficient antitumor response.
Descripción: Publicación ISIEmail : Hfsalazar@inmunotron.med.uchile.cl
URI: http://www.captura.uchile.cl/handle/2250/4901
Fecha: 2007
Cita del item: JOURNAL OF IMMUNOLOGY Vol. 178 01/06/2001 2007 11 6949-6957


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