title: Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells.
abstract: 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.
authors.affiliation: Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Mendoza-Naranjo
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Saéz
authors.forename: C Christian
authors.initials: CC
authors.lastname: Johansson
authors.forename: Marcos
authors.initials: M
authors.lastname: Ramírez
authors.forename: Dinka
authors.initials: D
authors.lastname: Mandakovic
authors.forename: Cristian
authors.initials: C
authors.lastname: Pereda
authors.forename: Mercedes N
authors.initials: MN
authors.lastname: López
authors.forename: Rolf
authors.initials: R
authors.lastname: Kiessling
authors.forename: Juan C
authors.initials: JC
authors.lastname: Sáez
authors.forename: Flavio
authors.initials: F
authors.lastname: Salazar-Onfray
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005456:Fluorescent Dyes / Q000378:metabolism; D017629:Gap Junctions / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D005456:Fluorescent Dyes; D007546:Isoquinolines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; C017475:lucifer yellow