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Int. J. Mol. Sci. 2016, 17(9), 1525; doi:10.3390/ijms17091525

In Vitro Assessment of the Expression and T Cell Immunogenicity of the Tumor-Associated Antigens BORIS, MUC1, hTERT, MAGE-A3 and Sp17 in Uterine Cancer

1
Department of Oncology, Gynecologic Oncology, Campus Gasthuisberg, Sandra Tuyaerts, KU Leuven—University of Leuven, Herestraat 49 Box 818, B-3000 Leuven, Belgium
2
Department of Gynecology and Obstetrics, Division Gynecologic Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Academic Editor: Michael R. Hamblin
Received: 11 July 2016 / Revised: 24 August 2016 / Accepted: 30 August 2016 / Published: 9 September 2016
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Abstract

Background: While immunotherapy moved to the forefront of treatment of various cancers, it remains underexplored for uterine cancer. This might be due to the small patient population with advanced endometrial carcinoma and uterine sarcoma. Data about immunotherapeutic targets are scarce in endometrial carcinoma and lacking in uterine sarcoma. Methods: Expression of five tumor-associated antigens (TAA) (BORIS, MUC1, hTERT, MAGE-A3 and Sp17) was validated in uterine tumor samples by immunohistochemistry (IHC) and/or quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). TAA immunogenicity was analyzed by determining spontaneous T cell responses towards overlapping peptide pools covering the whole TAA in patient blood. Results: At mRNA level, MAGE-A3 and Sp17 were overexpressed in a minority of patients and BORIS was moderately overexpressed (26% in endometrial carcinoma and 62% in uterine sarcoma). hTERT was overexpressed in the vast majority of tumors. On protein level, MUC1 was upregulated in primary, recurrent and metastatic EMCAR and in metastatic US tumors. hTERT protein was highly expressed in both normal and malignant tissue. Spontaneous TAA-specific T cell responses were detected in a minority of patients, except for hTERT to which T cell responses occurred more frequently. Conclusions: These data point to MUC1 and hTERT as most suitable targets based on expression levels and T cell immunogenicity for use in immunotherapeutic regimens. View Full-Text
Keywords: tumor-associated antigens; expression; immunogenicity; endometrial carcinoma; uterine sarcoma tumor-associated antigens; expression; immunogenicity; endometrial carcinoma; uterine sarcoma
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Vanderstraeten, A.; Tuyaerts, S.; Everaert, T.; Van Bree, R.; Verbist, G.; Luyten, C.; Amant, F. In Vitro Assessment of the Expression and T Cell Immunogenicity of the Tumor-Associated Antigens BORIS, MUC1, hTERT, MAGE-A3 and Sp17 in Uterine Cancer. Int. J. Mol. Sci. 2016, 17, 1525.

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