HLA-DR signaling inhibits Fas-mediated apoptosis in A375 melanoma cells

Aoudjit, Fawzi; Guo, Wenyan; Gagnon-Houde, Jean-Vincent; Castaigne, Jean‐Gabriel; Alcaïde‐Loridan, Catherine; Charron, Dominique; Al-Daccak, Reem

doi:10.1016/j.yexcr.2004.05.011

Cited by 21 publications

(25 citation statements)

References 57 publications

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“…Our results do not exclude that MAPK/ERK pathway activates additional survival mechanisms likely to be important in the resistance to Fas-induced apoptosis. We have recently shown that activation of ERK inhibits Fas-induced apoptosis in the Fas-sensitive A375 melanoma cell line by reducing activation of caspase-8 (69). Activated ERK can also reduce the release of the apoptogenic factor Smac/ DIABLO from the mitochondria, allowing the activation of IAP proteins and, thereby, inhibition of executioner caspases, an event implicated in the resistance to TRAIL-induced apoptosis (31).…”

Section: Discussionmentioning

confidence: 99%

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Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Chetoui

Sylla

Gagnon-Houde

et al. 2008

Molecular Cancer Research

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Resistance of malignant melanoma cells to Fas-mediated apoptosis is among the mechanisms by which they escape immune surveillance. However, the mechanisms contributing to their resistance are not completely understood, and it is still unclear whether antiapoptotic Bcl-2 -related family proteins play a role in this resistance. In this study, we report that treatment of Fas-resistant melanoma cell lines with cycloheximide, a general inhibitor of de novo protein synthesis, sensitizes them to anti-Fas monoclonal antibody (mAb) -induced apoptosis. The cycloheximide-induced sensitization to Fas-induced apoptosis is associated with a rapid down-regulation of Mcl-1 protein levels, but not that of Bcl-2 or Bcl-xL. Targeting Mcl-1 in these melanoma cell lines with specific small interfering RNA was sufficient to sensitize them to both anti-Fas mAb-induced apoptosis and activation of caspase-9.

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Section: Discussionmentioning

confidence: 99%

“…Expression of Fas receptor on melanoma cells was determined by staining the cells with FITC-conjugated anti-Fas mAb (UB2) and FACS analysis as we previously described (69).…”

Section: Fas Expression and Flow Cytometrymentioning

confidence: 99%

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Chetoui

Sylla

Gagnon-Houde

et al. 2008

Molecular Cancer Research

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“…Another peculiarity of some human melanoma cells is their ability to constitutively express MHCII and this is often associated with a poor prognosis (D'Alessandro et al, 1987;Martins et al, 2009;Ostmeier et al, 2001). Immune escape mediated by this alteration has been proposed as a possible explanation for worsening of the tumour phenotype (Aoudjit et al, 2004). In some circumstances however, CD4+ T-cells are able to kill MHCII positive melanocytes in vitro so the full effect of this anomaly is far from understood (Brady et al, 2000) and, currently, no studies evaluating this aberration have been undertaken for CMM.…”

Section: Possible Immunological Reasons For Lack Of Efficacymentioning

confidence: 99%

Cancer immunology and canine malignant melanoma: A comparative review

Atherton

Morris

McDermott

et al. 2016

Veterinary Immunology and Immunopathology

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Canine melanoma as a model of human melanomaFor at least two decades, veterinary oncologists have advocated using spontaneously occurring tumours in companion animals as models for human cancer (Knapp and Waters, 1997;MacEwen, 1990). Several recent reviews have readdressed this approach identifying osteosarcoma, mammary tumours, head and neck cancers, bladder carcinomas, non-Hodgkin lymphoma, prostatic carcinoma, lung cancer and pertinently oral canine malignant melanoma (CMM) as good models for human neoplasms (Hansen and Khanna, 2004;Khanna and Hunter, 2005;Paoloni and Khanna, 2008). The major benefits of dogs as tumour models include the ability to study genetically outbred and immunologically intact animals in which cancers develop spontaneously and thus, more likely reflect the process of tumourigenesis compared to experimentally-induced neoplasms. As pets and owners share the same environment, they may be exposed to the same carcinogens, which, in part, drive tumour development. Regarding disease modelling, animal tumours often have similar clinical presentation, tumour biology and histopathological appearance to their human counterparts and usually progress more rapidly, thereby shortening data maturation times. In addition, few "standard of care" therapies exist for dogs meaning that within reason, trial therapeutics can be instigated at any point. Given these benefits, companion animal tumour models more accurately reflect the features of human cancers compared to rodent models with CMM being a desirable example of one such neoplasm. Conversely, the opportunity to translate the potential value of state of the art human therapeutics to the veterinary clinic also exists. Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics.

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“…They are also receptors, which by triggering a variety of signaling pathways regulate APC activity (8). The exact role that MHC II might have in melanoma progression is unclear; it was suggested that MHC II can be involved in the escape of melanoma cells from immune surveillance through their capacity to present tumor Ags that activate regulatory T cells (Tregs) and/or through transmitting signals in melanoma cells that can protect against apoptosis (9,10). In support, it has been shown in melanoma patients that the CD4 + CD25…”

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confidence: 99%

“…Moreover, ligation of HLA-DR molecules expressed on A375 melanoma cells by the specific anti-HLA-DR mAb L243 inhibits Fas-mediated apoptosis through activation of the MAPK/Erk survival pathway (10). Notably, T cells infiltrating melanoma lesions express the natural physiological ligand of MHC II, namely the lymphocyte activation gene-3 (LAG-3 [CD223]) (12).…”

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confidence: 99%

MHC Class II Engagement by Its Ligand LAG-3 (CD223) Contributes to Melanoma Resistance to Apoptosis

Hémon

Jean-Louis

Ramgolam

et al. 2011

The Journal of Immunology

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Melanoma is the most aggressive skin cancer in humans that often expresses MHC class II (MHC II) molecules, which could make these tumors eliminable by the immune system. However, this MHC II expression has been associated with poor prognosis, and there is a lack of immune-mediated eradication. The lymphocyte activation gene-3 (LAG-3) is a natural ligand for MHC II that is substantially expressed on melanoma-infiltrating T cells including those endowed with potent immune-suppressive activity. Based on our previous data showing the signaling capacity of MHC II in melanoma cells, we hypothesized that LAG-3 could contribute to melanoma survival through its MHC II signaling capacity in melanoma cells. In this study, we demonstrate that both soluble LAG-3 and LAG-3–transfected cells can protect MHC II-positive melanoma cells, but not MHC II-negative cells, from FAS-mediated and drug-induced apoptosis. Interaction of LAG-3 with MHC II expressed on melanoma cells upregulates both MAPK/Erk and PI3K/Akt pathways, albeit with different kinetics. Inhibition studies using specific inhibitors of both pathways provided evidence of their involvement in the LAG-3–induced protection from apoptosis. Altogether, our data suggest that the LAG-3–MHC II interaction could be viewed as a bidirectional immune escape pathway in melanoma, with direct consequences shared by both melanoma and immune cells. In the future, compounds that efficiently hinder LAG-3–MHC II interaction might be used as an adjuvant to current therapy for MHC II-positive melanoma.

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HLA-DR signaling inhibits Fas-mediated apoptosis in A375 melanoma cells

Cited by 21 publications

References 57 publications

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Down-Regulation of Mcl-1 by Small Interfering RNA Sensitizes Resistant Melanoma Cells to Fas-Mediated Apoptosis

Cancer immunology and canine malignant melanoma: A comparative review

MHC Class II Engagement by Its Ligand LAG-3 (CD223) Contributes to Melanoma Resistance to Apoptosis

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