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

Mendoza-Naranjo A., Saéz P.J., Johansson C.C., Ramirez M., Mandakovic D., Pereda C., Lopez M.N., Kiessling R., Saéz J.C., Salazar-Onfray F.
J Immunol. 2007 Jun 1; 178(11):6949-57.

Previously, we found that human dendritic cells (hDCs) pulsed with a melanoma cell lysate (MCL) and stimulated with TNF-alpha (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.

URL: http://www.jimmunol.org/cgi/content/full/178/11/6949

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/17513744

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