Immunohistochemical expression of tumor antigens MAGE‐A1, MAGE‐A3/4, and NY‐ESO‐1 in cancerous and benign prostatic tissue

Hudolin, Tvrtko; António, José; Spagnoli, Giulio C.; Pasini, Josip; Bandic, Daniela; Heberer, Michael; Kosicek, M; Čačić, Marko

doi:10.1002/pros.20312

Cited by 35 publications

(26 citation statements)

References 18 publications

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“…An alternative possibility is that the MAGE-A6 peptides evaluated bare sufficient sequence or conformational homologies to proteins present in the environment to which many individuals may have become naturally primed against, allowing for functional cross-reactivity to be detected in our assays. This type of phenomenon has been previously suggested for the HLA-A2 -presented MART-1 [27][28][29][30][31][32][33][34][35] + Tcell responses against MAGE-A6 peptides predicted to be promiscuously presented by HLA-DR alleles and naturally processed rMAGE epitopes. CD4 + Tcells were isolated from the indicated (A) 14 melanoma patients and (B) 7 normal donors and tested for their ability to be stimulated by, and react against, the indicated MAGE-A6 peptides.…”

Section: Cd4mentioning

confidence: 59%

“…Diseases such as viral myocarditis, lyme disease, rheumatoid arthritis (45), multiple sclerosis (46), and virus-induced autoimmune diabetes (47,48) have long been considered to be initiated or exacerbated by microbial pathogens. As was previously noted for the HLA-A2 -presented, melanomaassociated MART-1 [27][28][29][30][31][32][33][34][35] epitope (35), we hypothesized that the high degree of normal donor response against the MAGE-A6 Th peptides might be due to the cross-reactivity of T cells initially primed in vivo against highly homologous peptides within environmentally encountered proteins. After performing a homology search of the GenBank database, we selected the MPHF2 216-229 and CHP [42][43][44][45][46][47][48][49][50][51][52][53][54][55] peptides as two likely candidate homologues of the MAGE-A6 172-187 and MAGE-A6 280-302 peptides, respectively.…”

Section: Discussionmentioning

confidence: 88%

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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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Section: Cd4mentioning

confidence: 59%

Section: Discussionmentioning

confidence: 88%

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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“…In urothelial TCC, a clear association between mRNA expression and grade was reported, with a progressive increase in frequency from 0% in grade 1 tumours to 44% in grade 4 tumours. 42 This contrasts with prostate cancer where no clear relationship was seen between IHC detection of NY-ESO-1 and LAGE-1, prostate specific antigen (PSA) or Gleason score, 29 although further evaluation in prostate cancer is warranted because patient selection in this study excluded those with a Gleason score of 8 or higher and expression has previously been shown to be more prevalent in metastatic prostate cancer. 41 In ovarian cancer, higher frequencies of NY-ESO-1 expression were found in serous carcinomas, whereas tumours of borderline malignancy or cystadenomas were negative.…”

Section: Factors Affecting Ny-eso-1 Expression In Tumoursmentioning

confidence: 87%

“…27 The majority of formalin-fixed tumour specimens display a heterogeneous cytoplasmic pattern of staining of NY-ESO-1 Ag. 4,28,29 It is not known whether heterogenous expression is a stable trait or varies over time (i.e., those cells that fail to stain at one time may nonetheless express Ag at some other time point). This will have implications for the interpretation of IHC results and hence patient eligibility for vaccination.…”

mentioning

confidence: 99%

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

et al. 2006

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Summary Since the early 1990s, numerous cancer Ag have been defined and for a handful of these there is now some clinical experience, which has made it possible to assess their value as targets for cancer immunotherapy. The cancer-testis Ag have been particularly attractive because their expression is limited to cancer and virtually no nonmalignant cells apart from germ cells and trophoblast. Among these, NY-ESO-1 has been the focus of our attention. The exceptional immunogenicity of this Ag coupled with its widespread distribution among many cancer types make it a very good vaccine candidate, with the potential to be used in vaccines against many types of malignancies. This article reviews emerging knowledge about the biology of NY-ESO-1 and experience with the early clinical development of vaccines directed against NY-ESO-1. These early studies have yielded a wealth of information about the immunology of NY-ESO-1 and set the scene for future clinical strategies for immune targeting of cancer.Key words: cancer immunology, cancer-testis Ag, cancer vaccine, dendritic cell, ISCOMATRIX, NY-ESO-1. Biology of NY-ESO-1NY-ESO-1 was first discovered using 'SERological identification of antigens by recombinant EXpression cloning' (SEREX). This is a method used for identifying the antibody repertoire of cancer-bearing patients by screening their serum against an expression library that typically displays protein Ag derived from a cancer source such as an autologous tumour or a cell line. In this case, NY-ESO-1 was found by using serum from a patient with squamous cell carcinoma (SCC) of the oesophagus. 1,2 Expression of NY-ESO-1 protein has been shown in multiple cancer types (Table 1), as well as in spermatogonia, oogonia and placenta. 3,4 Although NY-ESO-1 mRNA expression has been detected at low levels in some other normal tissues, it is unclear whether this is significant in the absence of detectable protein. 4,5 Other genes with similar names (NY-ESO-2, -3, -4, -5, -6, -7, -8) have no homology with NY-ESO-1. 2 The NY-ESO-1 gene is located on chromosome Xq28, 1 which carries a disproportionately high number of cancertestis (CT) Ag genes. 6 Up to 10% of the genes on chromosome X are CT Ag genes. The expression of these genes seems to be related to the demethylation of the promoter regions because experimental demethylation leads to the upregulation of CT Ag expression. [7][8][9][10][11][12][13][14][15][16][17][18] The NY-ESO-1 gene encodes a protein of 180 amino acids with M r 18 kDa, 2 which is expressed primarily in the cytoplasm although nuclear expression can be seen in some spermatogonia. 4 A homologue of NY-ESO-1, termed LAGE-1, was identified using representational difference analysis. 14 LAGE-1 and NY-ESO-1 are 84-89% homologous at the protein level. 14 Alternative splicing of LAGE-1 mRNA leads to the expression of two major transcripts encoding proteins of 210 and 180 amino acids, respectively. LAGE-1 is expressed in a wide variety of cancers (Table 1), usually, but not always, in conjunction with NY-ESO-1 or ...

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“…34 Further, NY-ESO-1 expression was also found in biopsies from 3% of localized prostate cancer and 15% of hormone refractory prostate cancer patients by immunohistochemistry. 35 Lethe et al 36 reported that expression of MAGE-A1 was observed in 10.8% of carcinoma samples, whereas multi-MAGE-A and NY-ESO-1/LAGE-1 stained 85.9% and 84.8% of samples using immunohistochemistry, suggesting that a panel of CTAs rather than individual ones maybe more valuable as biomarkers. Recently, Smith et al 37 showed that SSX protein expression was restricted mainly to metastatic prostate cancer and not expressed in any primary prostate cancer using immunohistochemistry.…”

Section: Ctas As Potential Biomarkers In Prostate Cancermentioning

confidence: 99%

Cancer/testis antigens: novel tools for discerning aggressive and non-aggressive prostate cancer

Shiraishi¹,

Getzenberg²,

Kulkarni³

2012

Asian J Androl

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Immunohistochemical expression of tumor antigens MAGE‐A1, MAGE‐A3/4, and NY‐ESO‐1 in cancerous and benign prostatic tissue

Abstract: Our data underline the peculiar relevance of cancer testis antigens expression in prostate cancers, with potential implications regarding both diagnosis and therapy.

Cited by 35 publications

References 18 publications

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

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

Directions in the immune targeting of cancer: Lessons learned from the cancer‐testis Ag NY‐ESO‐1

Cancer/testis antigens: novel tools for discerning aggressive and non-aggressive prostate cancer

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