Gap Junctions Intercellular communication participates in CD8+ T cells-mediated cytotoxicity against melanoma
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1
Universidad de Chile, Institute of Biomedical Sciences, Chile
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2
Millennium Institute on Immunology and Immunotherapy, Chile
Introduction: Gap Junction intercellular communications (GJIC) are involved in important aspects of cell biology, particularly in the control of proliferation, differentiation and apoptosis. Each Gap Junction (GJ) channel is formed by two structures called connexons. Each connexon is composed of 6 subunits, called connexin (Cx) being the Cx43 the most expressed in mammals. Previously, we demonstrated that GJs are important in cytotoxic processes including antitumor response by human NK cells. Nevertheless, the role of Gap Junction in cell communication between CD8+ T cells and cancer cells remains unexplored. In this study, we analyzed the role of GJICs in CD8+ T cell communication and cytotoxicity against human melanoma cells. Material and Methods: Using immunofluorescence techniques, we evaluated the localization of Cx43 plaques in co-cultures between CD8+ T cells and melanoma cells. Gap Junctions functionality was evaluated by intercellular transfer of Calcein-AM (cell tracker) by Flow Cytometry and release of Cr51 by tumor cells as readout of the cytotoxic activity. Results: We found polarization of Cx43 at the CD8+ T cells/tumor cell-contact sites, accompanied by the formation of functional GJs between CD8+ T cells and tumor cells, respectively. Blockade of Cx43-GJIC with reported Cx inhibitors decreased the activation of effector cells and Calcein-AM transfer from the donor to acceptor cells. Moreover, blocking Cx43 strongly inhibited CD8+ T cells–mediated tumor cell lysis associated with inhibition of granzyme B activity and Ca2+ influx. Discussion: We demonstrated that the Cx43-GJs are important for the modulation of CD8+ T cells cytotoxicity activity against human melanoma cells, which may be of relevance for the understanding of cytotoxic processes during an antitumor response and the designing of novel immunotherapeutic strategies.
Acknowledgements
Funded by grants FONDECYT-1130320 and 1130324; FONDEF-D11I1036 and IMII P09/016-F.
Keywords:
Melanoma,
Connexin 43,
Gap Junctions,
Cytotoxic T Cells,
hemichannels
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Tumor immunology
Citation:
Lillo Vera
FA,
Gleisner
MA,
Guerrero
I,
Lopez
MN and
Salazar Onfray
FA
(2015). Gap Junctions Intercellular communication participates in CD8+ T cells-mediated cytotoxicity against melanoma.
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00062
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Received:
15 May 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
PhD. Flavio A Salazar Onfray, Universidad de Chile, Institute of Biomedical Sciences, Santiago, Chile, flavio.salazar@inmunotron.med.uchile.cl