Functional Gap Junctions Facilitate Melanoma Antigen Transfer and Cross-Presentation between Human Dendritic Cells

  • Mendoza-Naranjo A
  • Saéz P
  • Johansson C
  • et al.
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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.

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APA

Mendoza-Naranjo, A., Saéz, P. J., Johansson, C. C., Ramírez, M., Mandaković, D., Pereda, C., … Salazar-Onfray, F. (2007). Functional Gap Junctions Facilitate Melanoma Antigen Transfer and Cross-Presentation between Human Dendritic Cells. The Journal of Immunology, 178(11), 6949–6957. https://doi.org/10.4049/jimmunol.178.11.6949

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