Functional gap junctions facilitate melanoma antigen transfer and cross-presentation between human dendritic cells.
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.
Mendoza-Naranjo
Ariadna
A
Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Saéz
Pablo J
PJ
Johansson
C Christian
CC
Ramírez
Marcos
M
Mandakovic
Dinka
D
Pereda
Cristian
C
López
Mercedes N
MN
Kiessling
Rolf
R
Sáez
Juan C
JC
Salazar-Onfray
Flavio
F
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
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