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.
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.
Department of Oncology, Gynecologic Oncology, Campus Gasthuisberg, Sandra Tuyaerts, KU Leuven-University of Leuven, Herestraat 49 Box 818, B-3000 Leuven, Belgium. anke.vanderstraeten@gmail.com.
Anke
A
Vanderstraeten
Department of Oncology, Gynecologic Oncology, Campus Gasthuisberg, Sandra Tuyaerts, KU Leuven-University of Leuven, Herestraat 49 Box 818, B-3000 Leuven, Belgium. sandra.tuyaerts@uzleuven.be.
Sandra
S
Tuyaerts
Department of Oncology, Gynecologic Oncology, Campus Gasthuisberg, Sandra Tuyaerts, KU Leuven-University of Leuven, Herestraat 49 Box 818, B-3000 Leuven, Belgium. tina.everaert@uzleuven.be.
Tina
T
Everaert
Department of Oncology, Gynecologic Oncology, Campus Gasthuisberg, Sandra Tuyaerts, KU Leuven-University of Leuven, Herestraat 49 Box 818, B-3000 Leuven, Belgium. rita.vanbree@kuleuven.be.
Rieta
R
Van Bree
Department of Gynecology and Obstetrics, Division Gynecologic Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. godelieve.verbist@kuleuven.be.
Godelieve
G
Verbist
Department of Oncology, Gynecologic Oncology, Campus Gasthuisberg, Sandra Tuyaerts, KU Leuven-University of Leuven, Herestraat 49 Box 818, B-3000 Leuven, Belgium. katrien.luyten@kuleuven.be.
Cathérine
C
Luyten
Department of Oncology, Gynecologic Oncology, Campus Gasthuisberg, Sandra Tuyaerts, KU Leuven-University of Leuven, Herestraat 49 Box 818, B-3000 Leuven, Belgium. frederic.amant@uzleuven.be.|Department of Gynecology and Obstetrics, Division Gynecologic Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. frederic.amant@uzleuven.be.
Frederic
F
Amant
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D008565:Membrane Proteins; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D012509:Sarcoma / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C456540:CTCFL protein, human; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C072013:MAGEA3 protein, human; C060192:MUC1 protein, human; D008565:Membrane Proteins; D018396:Mucin-1; D009363:Neoplasm Proteins; D010455:Peptides; C090172:SPA17 protein, human; C509186:TERT protein, human; D019098:Telomerase
endometrial carcinoma; expression; immunogenicity; tumor-associated antigens; uterine sarcoma