Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen ny-eso-1 but not mage-a1 or ct7

Jungbluth, Achim A.; Antonescu, Cristina R.; Busam, Klaus J.; Iversen, Kristin; Kolb, Denise; Coplan, Keren; Chen, Yao T.; Stockert, Elisabeth; Ladanyi, Marc; Old, Lloyd J.

doi:10.1002/ijc.1451

Cited by 176 publications

(150 citation statements)

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“…18,21,22 Synovial sarcomas, which exhibited a high expression of MAGE and NY-ESO-1, 21,22 revealed little CT7-33 reactivity, as found in a recent analyses of 25 cases. 23 Carcinomas of the head and neck also exhibited poor CT7 protein expression in our study, which contradicts original RT-PCR analyses. 10,11 However, a larger number of these tumors need to be evaluated before a final conclusion about their expression pattern can be reached.…”

Section: Discussioncontrasting

confidence: 99%

CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues

Jungbluth

Chen

Busam

et al. 2002

Intl Journal of Cancer

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CT7 (MAGE-C1) is a member of the cancer testis (CT)antigen family. The present study describes the generation of CT7-33, a monoclonal antibody (MAb) to CT7, and the preliminary protein expression analysis of CT7 in normal tissues and in a limited number of neoplastic lesions. CT7-33 was effective in frozen as well as formalin-fixed, paraffin-embedded tissues, and immunohistochemistry/reverse transcriptase polymerase chain reaction (RT-PCR) co-typing demonstrated antibody specificity. CT7-33 immunoreactivity in normal adult tissues is restricted to testicular germ cells. In neoplastic lesions, CT7-33 immunostaining is confined to tumor cells, and the frequency of CT7 protein expression mostly parallels previous mRNA analyses. Whereas colorectal and renal cell carcinomas, as well as sarcomas, exhibit poor or no CT7-33 staining, carcinomas of the mammary gland and ovary, nonsmall cell lung carcinoma and metastatic melanomas exhibit a high incidence of CT7 protein expression. However, as seen in previous analyses of other CT antigens, the expression pattern is mostly heterogeneous, and tumors with more than 50% of tumor staining are only infrequently encountered. In summary, our study Key words: CT7; MAGE-C1; heterogeneous antigen expression; monoclonal antibody CT7-33Cancer testis (CT) antigens are expressed in a variety of malignant neoplasms but not in normal adult tissues except for germ cells of the testis. 1,2 Due to their expression pattern, CT antigens appear to be ideal targets for immunotherapeutic strategies against malignant neoplasms. Since the isolation of the prototype CT gene family, MAGE, the number of CT antigens has steadily increased. 3 Whereas autologous T-cell epitope cloning was used for the initial identification of CT antigens such as MAGE and BAGE, 4,5 others have been isolated by SEREX (serological analysis of recombinant cDNA expression libraries) analysis. SEREX employs the immunologic screening of cDNA expression libraries from human tumors with autologous patient sera. 6 -9 By using the SEREX approach, we recently identified CT7, 10 a new member of the CT family. The same gene was isolated independently by Lucas et al. 11 using representational difference analysis (RDA) and termed MAGE-C1. A preliminary RT-PCR analysis revealed the presence of CT7 (MAGE-C1) in normal testis and in a variety of neoplasms, such as melanoma, and tumors of the urinary bladder, breast and lung. To assess CT7 as a potential target for immunotherapy, analysis of its actual antigen expression is essential. The present study describes the generation of the monoclonal antibody (MAb) CT7-33 to CT7 (MAGE-C1) and an immunohistochemical analysis of CT7 (MAGE-C1) expression in normal and tumorous tissues. MATERIAL AND METHODS Production of recombinant CT7 proteinA truncated CT7 product was chosen for the expression in E. coli. This truncated form encoded 350 of 1,124 amino acids in the CT7 antigen, namely positions 552-901. The purpose of this truncation was to exclude the C-terminus, which shares significant homolo...

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Section: Discussioncontrasting

confidence: 99%

CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues

Jungbluth

Chen

Busam

et al. 2002

Intl Journal of Cancer

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“…Among all STS samples, we found a significant correlation between both the T‐cell fraction and clonality with PD‐1 and PD‐L1 expression regardless of STS subtype. This association was true across a diverse set of tumors, including highly mutated UPS as well as the genetically simpler SS and MRCL tumors 15, 16. This observation supports the suggestion that inflamed tumors are better targets for checkpoint inhibition.…”

Section: Discussionsupporting

confidence: 78%

T‐cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death‐ligand 1 expression in patients with soft tissue sarcomas

Pollack

Yearley

et al. 2017

Cancer

222

203

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BACKGROUNDPatients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited.METHODSThe authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well‐differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD‐1) and programmed death‐ligand 1 (PD‐L1), and T‐cell receptor Vβ gene sequencing were performed on formalin‐fixed, paraffin‐embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated.RESULTSUPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T‐cell infiltration. UPS were found to have higher levels of PD‐L1 (P≤.001) and PD‐1 (P≤.05) on immunohistochemistry and had the highest T‐cell infiltration based on T‐cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T‐cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T‐cell infiltration and clonality were highly correlated with PD‐1 and PD‐L1 expression levels (P≤.01).CONCLUSIONSIn the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self‐antigens, and therefore strategies to improve antigen presentation and T‐cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291‐304. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…The development of novel systemic therapies is important because metastasis of synovial sarcoma is common (overall 5-year metastasis-free survival rate 51.1%). 30 Jungbluth et al 31 49.3% positivity across 69 cases of synovial sarcoma, somewhat lower than that of the previous papers, possibly because of the decreased sensitivity using the tissue microarray platform. Considering the combined results from our and previous studies, approximately half to three quarters of synovial sarcomas show NY-ESO-1 expression.…”

Section: Ny-eso-1 In Mesenchymal Tumorsmentioning

confidence: 61%

NY-ESO-1 (CTAG1B) expression in mesenchymal tumors

et al. 2015

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New York esophageal squamous cell carcinoma 1 (NY-ESO-1, CTAG1B) is a cancer-testis antigen and currently a focus of several targeted immunotherapeutic strategies. We performed a large-scale immunohistochemical expression study of NY-ESO-1 using tissue microarrays of mesenchymal tumors from three institutions in an international collaboration. A total of 1132 intermediate and malignant and 175 benign mesenchymal lesions were enrolled in this study. Immunohistochemical staining was performed on tissue microarrays using a monoclonal antibody for NY-ESO-1. Among mesenchymal tumors, myxoid liposarcomas showed the highest positivity for NY-ESO-1 (88%), followed by synovial sarcomas (49%), myxofibrosarcomas (35%), and conventional chondrosarcomas (28%). Positivity of NY-ESO-1 in the remaining mesenchymal tumors was consistently low, and no immunoreactivity was observed in benign mesenchymal lesions. On the basis of these findings, nearly 90% of myxoid liposarcomas, as well as a significant proportion of synovial sarcomas, myxofibrosarcomas, and conventional chondrosarcomas are good candidates for immunotherapy targeting NY-ESO-1. Modern Pathology (2015) 28, 587-595; doi:10.1038/modpathol.2014.155; published online 21 November 2014New York esophageal squamous cell carcinoma 1 (NY-ESO-1), encoded by the CTAG1B gene, is a cancer-testis antigen that was identified in 1997 from the serum of a patient with esophageal squamous cell carcinoma. 1 Cancer-testis antigens such as NY-ESO-1 have attracted increasing attention as immunotherapeutic targets because, among normal tissues, they are expressed only in adult testis germ cells and are atypically re-expressed in many malignancies. 2,3 NY-ESO-1 is of particular interest to researchers and clinicians because it is highly immunogenic and is expressed in a variety of carcinomas, melanomas, and sarcomas. 4 A recent clinical trial of adoptive immunotherapy, using genetically modified T cells directed against NY-ESO-1, demonstrated objective clinical responses in a number of metastatic synovial sarcoma and melanoma patients with NY-ESO-1-positive tumors. 5 The results of that clinical trial highlight the potential effectiveness of immunotherapy against tumors expressing NY-ESO-1, and several clinical trials (using antigen sensitization, adoptive T-cell transfer, and dendritic cell vaccine strategies) are currently underway.Mesenchymal tumors arising from bone or soft tissues comprise many histologic subtypes, which even when taken together occur at a much lower rate than the more common carcinomas, creating a practical barrier to developing new drug therapies. However, the well-defined biology of many sarcomas suggests they may be particularly susceptible to appropriate targeted strategies. Recent studies have reported NY-ESO-1 expression in an especially large proportion of myxoid liposarcomas and synovial sarcomas. 2,6-9 These studies also revealed the

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Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen ny-eso-1 but not mage-a1 or ct7

Cited by 176 publications

References 44 publications

CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues

CT7 (MAGE‐C1) antigen expression in normal and neoplastic tissues

T‐cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death‐ligand 1 expression in patients with soft tissue sarcomas

NY-ESO-1 (CTAG1B) expression in mesenchymal tumors

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