Expression of cancer/testis (CT) antigens in squamous cell carcinoma of the head and neck: Evaluation as markers of squamous dysplasia

Piotti, Kathryn C.; Scognamiglio, Theresa; Chiu, Rita; Chen, Yao‐Tseng

doi:10.1016/j.prp.2013.08.004

Cited by 20 publications

(15 citation statements)

References 28 publications

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“…Because squamous cell carcinoma is the main type of smoking-related carcinoma in the major airways, it is possible that squamous cell carcinoma might represent a special tumor type in which the cancer-testis gene activation is often an early event. We have recently analyzed squamous cell carcinoma and dysplasia in the head and neck region, and cancer-testis antigens were similarly observed in a subset of squamous dysplasia (39), further supporting this possibility. This would suggest that cancer-testis antigens could be useful markers of early malignant transformation in squamous cell carcinogenesis, and it would be worthwhile to explore this possibility in a prospective study of dysplastic squamous lesions with long-term follow-up.…”

Section: Discussionmentioning

confidence: 58%

Cancer–Testis Antigen Expression in Digestive Tract Carcinomas: Frequent Expression in Esophageal Squamous Cell Carcinoma and Its Precursor Lesions

Chen

Panarelli

Piotti

et al. 2014

Cancer Immunology Research

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Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions. Cancer Immunol Res; 2(5); 480-6. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 58%

Cancer–Testis Antigen Expression in Digestive Tract Carcinomas: Frequent Expression in Esophageal Squamous Cell Carcinoma and Its Precursor Lesions

Chen

Panarelli

Piotti

et al. 2014

Cancer Immunology Research

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“…risk of lymph node metastasis at the initial presentation, RFS, and DSS. In addition, multiple previous studies have investigated the rate and prognostic significance of CTA expression in HNSCC, and have shown a high rate of CTA expression in these tumours but inconsistent prognostic significance . Taken together, these data indicate that CTAs, e.g.…”

Section: Discussionmentioning

confidence: 65%

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Jungbluth

Frosina

et al. 2019

Histopathology

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Aims Salivary duct carcinoma (SDC) is an aggressive salivary malignancy that results in high mortality rates and is often resistant to chemotherapy. Anti‐programmed death‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) checkpoint inhibitors have led to dramatic improvements in patients with various cancers. Other immunotherapeutic approaches, e.g. cancer vaccines, have shown promising results. Cancer testis antigens, e.g. preferentially expressed antigen in melanoma (PRAME), are regarded as promising vaccine targets because of their tumour‐specific expression pattern. Methods and results We analysed the immunoexpression of PD‐L1, PD‐1, major histocompatibility complex class I (MHC I) and PRAME in 53 SDCs. The immunoexpression levels of PD‐L1 in tumour cells (TCs) and immune cells (ICs), PD‐1 in ICs, PRAME in TCs and MHC I in TCs were analysed, and were correlated with outcome. PRAME expression was seen in 83% of SDCs. No PRAME staining was present in normal salivary gland tissue. With the three established diagnostic algorithms proposed for head and neck squamous cell carcinoma, the criteria being a combined positive score of ≥1, TC% ≥1%, and TC% ≥25%, 35 (66%), 17 (32%) and three cases (6%), respectively, were deemed to be positive for PD‐L1. PD‐1‐positive ICs were seen in 35 (66%) cases. MHC I down‐regulation was seen in 82% of SDCs. There was a significant correlation among PD‐L1 expression in ICs, PD‐1 expression in ICs, and PRAME expression in TCs. PD‐L1 expression in TCs and lack of PD‐1 expression in ICs were associated with decreased disease‐specific survival in SDC patients. Conclusions Alterations of the tumour immune microenvironment are common in SDCs, including expression of PD‐1/PD‐L1 and PRAME, which opens the way to potential novel immune therapies, such as cancer vaccination and PD‐1/PD‐L1 blockade, in these tumours.

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“…This suggests that raising immunity to one or more of these antigens with a vaccine prior to any evidence of tumor would strengthen immunosurveillance and reduce risk, eventually replacing prophylactic mastectomies. CT antigens have also been found in squamous dysplasia leading to head and neck cancer, and squamous cell carcinoma in situ in esophageal biopsies [24,25], two other cancers that could be targeted for prevention in the premalignant stage.…”

Section: Candidate Antigens For Preventative Vaccinesmentioning

confidence: 99%

Cancer immunoprevention

Finn

Beatty

2016

Current Opinion in Immunology

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Cancer immunotherapy is now a reality. The results are phenomenal but the cost is outrageous. Even if the cost eventually comes down and immunotherapy becomes more broadly available, using the knowledge derived from immunotherapy to apply to immunoprevention would be a good strategy. The most likely approach to cancer immunoprevention is cancer vaccines. To date, cancer vaccines have been tested mostly in the setting of advanced disease. Numerous immunosuppressive mechanisms have been identified in the tumor microenvironment as well as systemically that compromise the ability of cancer patients to respond to the vaccines. Multiple approaches are being tested to improve therapeutic cancer vaccine efficacy, including combinations with other immunotherapies. An alternative approach is to administer the vaccines to individuals without cancer but at high risk for cancer. Data in support of this approach and immunoprevention in general is accumulating and clinical testing has started.

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Expression of cancer/testis (CT) antigens in squamous cell carcinoma of the head and neck: Evaluation as markers of squamous dysplasia

Cited by 20 publications

References 28 publications

Cancer–Testis Antigen Expression in Digestive Tract Carcinomas: Frequent Expression in Esophageal Squamous Cell Carcinoma and Its Precursor Lesions

Cancer–Testis Antigen Expression in Digestive Tract Carcinomas: Frequent Expression in Esophageal Squamous Cell Carcinoma and Its Precursor Lesions

The immune microenvironment and expression of PD‐L1, PD‐1, PRAME and MHC I in salivary duct carcinoma

Cancer immunoprevention

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