title: In Vitro Validation of Survivin as Target Tumor-associated Antigen for Immunotherapy in Uterine Cancer.
abstract: Survivin is an antiapoptotic protein, not expressed in terminally differentiated adult tissues, yet overexpressed in several tumors. Therefore, it is an interesting target for immunotherapeutic strategies. In addition to specific overexpression in tumors, tumor survival is mediated by survivin and hence, tumor survival can be tackled by targeting survivin. Survivin expression in uterine cancer was validated by quantitative real-time polymerase chain reaction and immunohistochemistry. In addition, we evaluated survivin immunogenicity by analyzing spontaneous B-cell and T-cell responses in patients. Survivin as a protein was expressed in only a minority of normal tissues, whereas it was being expressed in all of the currently analyzed uterine cancers, both endometrial carcinoma (n = 52) and uterine sarcoma (n = 52). Survivin RNA transcripts were overexpressed in more aggressive tumors and survivin protein was overexpressed in recurrent endometrial tumors compared with primary tumors. Spontaneous T-cell responses were seen in 10/39 endometrial cancer patients and 3/16 uterine sarcoma patients. In normal controls, T-cell responses were found only in 1 donor (n = 21). Although increased antibody titers were found in more aggressive and far-advanced tumors, no differences in B-cell responses were seen. Overall, when compared with normal controls, a B-cell response was only measured in 1/41 uterine sarcoma patients. In conclusion, we currently validated the presence of survivin in uterine cancer. In addition, spontaneous T-cell responses were found in 23.6% of the total patient population. These data indicate that a survivin-specific immune response may be induced spontaneously in patients, further fortifying the eligibility of survivin as an immunotherapeutic target.
authors.affiliation: *Department of Oncology, Gynecologic Oncology, KU Leuven-University of Leuven †Department of Gynecology and Obstetrics, Division Gynecologic Oncology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Anke
authors.initials: A
authors.lastname: Vanderstraeten
authors.forename: Tina
authors.initials: T
authors.lastname: Everaert
authors.forename: Rieta
authors.initials: R
authors.lastname: Van Bree
authors.forename: Godelieve
authors.initials: G
authors.lastname: Verbist
authors.forename: Cathérine
authors.initials: C
authors.lastname: Luyten
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: Sandra
authors.initials: S
authors.lastname: Tuyaerts
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016889:Endometrial Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins / Q000276:immunology*; D008213:Lymphocyte Activation; D058990:Molecular Targeted Therapy; D012509:Sarcoma / Q000276:immunology / Q000628:therapy*; D000077022:Survivin; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin