Immunohistological evaluation of MHC class I and II antigen expression on nevi and melanoma: relation to biology of melanoma

D'alessandro, G.; Hersey, Peter; Zardawi, Ibrahim M.; Grace, Julienne; McCarthy, William H.

doi:10.3109/00313028709103880

Cited by 36 publications

(12 citation statements)

References 21 publications

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“…On one hand, our results provide evidence that our previously reported MHC II-mediated hampering of the killing by immune cells is physiologically valid. On the other hand, they may provide one possible explanation into the growth advantage of MHC II-positive skin tumors (50) and into the longstanding correlation between MHC II expression and degree of melanoma malignancy (2,(5)(6)(7). However LAG-3 also protects from drug-induced apoptosis.…”

Section: Discussionmentioning

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

207

146

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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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Section: Discussionmentioning

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

207

146

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“…Although a proportion of solid cancers, including (up to 50-70% of) melanoma, have been reported to constitutively express MHC class II molecules in situ (38), even those that do not can frequently be induced to express class II complexes in vitro and in vivo after treatment with IFN-g (39,40). Hence, periodic inflammatory responses (accompanied by IFN-g production or by provision of IFN-g as a therapy) within the tumor microenvironment or tumor-draining lymph nodes have the potential to enforce tumor cells as relevant APCs for the priming or boosting of tumor antigen (such as MAGE-A6) -specific CD4 + and CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

A Mycoplasma Peptide Elicits Heteroclitic CD4+ T Cell Responses against Tumor Antigen MAGE-A6

Vujanović

Mandić²,

Olson³

et al. 2007

Clinical Cancer Research

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Purpose: Although T-helper (Th) epitopes have been previously reported for many tumor antigens, including MAGE-A6, the relevant HLA-DR alleles that present these peptides are expressed by only a minority of patients. The identification of tumor antigenic epitopes presented promiscuously by many HLA-DR alleles would extend the clinical utility of these peptides in vaccines and for the immunomonitoring of cancer patients. Experimental Design: A neural network algorithm and in vitro sensitization assays were employed to screen candidate peptides for their immunogenicity. Results: The MAGE-A6 14 0 -170 , MAGE-A6 172-187 , and MAGE-A6 280-302 epitopes were recognized by CD4 + T cells isolated from the majority of normal donors and melanoma patients evaluated. Peptide-specific CD4 + T cells also recognized autologous antigen-presenting cell pulsed with recombinant MAGE-A6 (rMAGE) protein, supporting the natural processing and MHC presentation of these epitopes. Given the strong primary in vitro sensitization of normal donor CD4 + T cells by the MAGEA6 172-187 epitope, suggestive of potential cross-reactivity against an environmental stimulus, we identified a highly homologous peptide within the Mycoplasma penetrans HF-2 permease (MPHF2) protein. MPHF2 peptide^primed CD4 + Tcells cross-reacted against autologous APC pulsed with the MAGE-A6 172-187 peptide or rMAGE protein and recognized HLA-matched MAGE-A6 + melanoma cell lines. These responses seemed heteroclitic in nature because the functional avidity of MPHF2 peptide-primed CD4 + Tcells for the MAGE-A6 172-187 peptide was f1,000 times greater than that of CD4 + T cells primed with the corresponding MAGE-A6 peptide. Conclusions: We believe that these novel ''promiscuous'' MAGE-A6/MPHF2 Th epitopes may prove clinically useful in the treatment and/or monitoring of a high proportion of cancer patients.

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“…It should be noted, however, that although these mRNA data are supportive of active gene transcription, one could not conclude that the encoded proteins are properly translated, proteolytically processed and correctly oriented within the cell, which is of key importance to effective antigen presentation (York and Rock, 1996). 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).…”

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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Immunohistological evaluation of MHC class I and II antigen expression on nevi and melanoma: relation to biology of melanoma

Cited by 36 publications

References 21 publications

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

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

A Mycoplasma Peptide Elicits Heteroclitic CD4+ T Cell Responses against Tumor Antigen MAGE-A6

Cancer immunology and canine malignant melanoma: A comparative review

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