Regulation of gap junctions in melanoma and their impact on Melan-A/MART-1-specific CD8+ T lymphocyte emergence

Benlalam, Houssem; Carré, Thibault; Jalil, Abdelali; Noman, Zaeem; Caillou, Bernard; Vielh, Philippe; Tittarelli, Andrés; Robert, Caroline; Chouaı̈b, Salem

doi:10.1007/s00109-013-1058-5

Cited by 9 publications

(7 citation statements)

References 34 publications

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“…It has been reported in vitro as well as in situ that human naïve CD8 + T cells establish GJCs with melanoma target cells, contributing to their activation, but not to their lytic function [240]. Conversely, human NK cells establish GJCs with DCs and tumor cells in a Cx43-dependent process that contributes to NK cell-mediated lysis and further antitumoral immunity (Figure 7) [107].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Hemichannels and Gap Junction Channels by Cytokines in Antigen-Presenting Cells

Saéz

Shoji

Aguirre

et al. 2014

Mediators of Inflammation

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Autocrine and paracrine signals coordinate responses of several cell types of the immune system that provide efficient protection against different challenges. Antigen-presenting cells (APCs) coordinate activation of this system via homocellular and heterocellular interactions. Cytokines constitute chemical intercellular signals among immune cells and might promote pro- or anti-inflammatory effects. During the last two decades, two membrane pathways for intercellular communication have been demonstrated in cells of the immune system. They are called hemichannels (HCs) and gap junction channels (GJCs) and provide new insights into the mechanisms of the orchestrated response of immune cells. GJCs and HCs are permeable to ions and small molecules, including signaling molecules. The direct intercellular transfer between contacting cells can be mediated by GJCs, whereas the release to or uptake from the extracellular milieu can be mediated by HCs. GJCs and HCs can be constituted by two protein families: connexins (Cxs) or pannexins (Panxs), which are present in almost all APCs, being Cx43 and Panx1 the most ubiquitous members of each protein family. In this review, we focus on the effects of different cytokines on the intercellular communication mediated by HCs and GJCs in APCs and their impact on purinergic signaling.

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Section: Discussionmentioning

confidence: 99%

Regulation of Hemichannels and Gap Junction Channels by Cytokines in Antigen-Presenting Cells

Saéz

Shoji

Aguirre

et al. 2014

Mediators of Inflammation

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“…NK92 and MCF7 cells were obtained from the ATCC. Cells were maintained in culture as described previously (7). NK cells were maintained in RPMI medium supplemented with 300 units/ml recombinant human IL-2.…”

Section: Methodsmentioning

confidence: 99%

“…Because Cxs have short half-lives, their turnover regulation and trafficking critically impact the control of GJmediated intercellular communication (5). Connexin 43 (Cx43), the main GJ protein found in immune cells (6), has been shown recently to accumulate at the immunological synapse and allows GJ-mediated intercellular communication between effector immune and tumor target cells (7)(8)(9)(10). These observations suggest that loss of Cx43 expression during tumor progression may represent a mechanism by which cancer cells evade immune control by the local microenvironment (11).…”

mentioning

confidence: 99%

The Selective Degradation of Synaptic Connexin 43 Protein by Hypoxia-induced Autophagy Impairs Natural Killer Cell-mediated Tumor Cell Killing

Tittarelli

Janji

Moer

et al. 2015

Journal of Biological Chemistry

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Background:The regulation of gap junction protein connexin 43 (Cx43), involved in natural killer (NK) cell-mediated tumor killing, is still elusive. Results: Hypoxia-induced autophagy selectively degrades gap junctional Cx43 from immune synapses and impairs NK-mediated melanoma cell lysis. Conclusion: A hypoxic microenvironment induces melanoma resistance to NK cells via modulation of Cx43 channels. Significance: Targeting autophagy prevents gap-junctional Cx43 degradation and potentiates NK-based tumor immunotherapies.

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“…In human melanoma biopsies, it has been demonstrated that Cx43 is expressed between tumor and endothelial cells and between T-cells and cancer cells, indicative of GJ formation [54]. This study proposed that GJs between these cells regulate the formation of an immunological synapse among T lymphocytes and autologous melanoma cells [106]. In this model, the opening of Cx43 HCs has been associated with cytokine release by T-cells and regulation of Ca 2+ oscillations among T cells.…”

Section: Expression Of Connexins and Pannexins In Immune Cellsmentioning

confidence: 99%

The role of connexin and pannexin containing channels in the innate and acquired immune response

Valdebenito¹,

Barreto²,

Eugenín³

2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Connexin (Cx) and pannexin (Panx) containing channels - gap junctions (GJs) and hemichannels (HCs) - are present in virtually all cells and tissues. Currently, the role of these channels under physiological conditions is well defined. However, their role in the immune response and pathological conditions has only recently been explored. Data from several laboratories demonstrates that infectious agents, including HIV, have evolved to take advantage of GJs and HCs to improve viral/bacterial replication, enhance inflammation, and help spread toxicity into neighboring areas. In the current review, we discuss the role of Cx and Panx containing channels in immune activation and the pathogenesis of several infectious diseases. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve.

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Regulation of gap junctions in melanoma and their impact on Melan-A/MART-1-specific CD8+ T lymphocyte emergence

Cited by 9 publications

References 34 publications

Regulation of Hemichannels and Gap Junction Channels by Cytokines in Antigen-Presenting Cells

Regulation of Hemichannels and Gap Junction Channels by Cytokines in Antigen-Presenting Cells

The Selective Degradation of Synaptic Connexin 43 Protein by Hypoxia-induced Autophagy Impairs Natural Killer Cell-mediated Tumor Cell Killing

The role of connexin and pannexin containing channels in the innate and acquired immune response

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