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

Mendoza-Naranjo, A; Sáez PJ; Johansson, CC; Ramirez M.; Mandakovic, D; Pereda, C; López MN; Kiessling R.; Sáez JC; SALAZAR ONFRAY F

Abstract

Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma cell lysate (MCL) and stimulated with TNF-α (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. Copyright © 2007 by The American Association of Immunologists, Inc.

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Título según WOS: Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells
Título según SCOPUS: Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells
Título de la Revista: JOURNAL OF IMMUNOLOGY
Volumen: 178
Número: 11
Editorial: AMER ASSOC IMMUNOLOGISTS
Fecha de publicación: 2007
Página de inicio: 6949
Página final: 6957
Idioma: English
Notas: ISI, SCOPUS