title: P53-specific T cell responses in patients with malignant and benign ovarian tumors: implications for p53 based immunotherapy.
abstract: Despite intensive treatment, 70% of the ovarian cancer patients will develop recurrent disease, emphasizing the need for new approaches such as immunotherapy. A promising antigenic target for immunotherapy in ovarian cancer is the frequently overexpressed p53 protein. The aim of the study was to evaluate the nature and magnitude of the baseline anti-p53 immune response in ovarian cancer patients. P53-specific T cell responses were detected in both half of the ovarian cancer patients as in the group of control subjects, consisting of women with benign ovarian tumors and healthy controls. Importantly, while in the control group p53-specific immunity was detected among the CD45RA(+) naïve subset of T cells only, the p53-specific T-cell responses in ovarian cancer patients were also present in the CD45RO(+) memory T-cell subset, suggesting that in the cancer patients sufficient amounts of cancer-derived p53 was presented to induce the formation of a p53-specific memory T-cell response. Further characterization of the p53-specific memory T-cell responses revealed that in addition to the type 1 cytokine IFN-gamma also the type 2 cytokines IL-4 and IL-5, as well as the immunosuppressive cytokine IL-10 were produced. Notably, p53-specific T cells were not only detected in the peripheral blood, but also among tumor infiltrating lymphocytes and in tumor-draining lymph nodes. In conclusion, the existence of a weak mixed T-helper type 1 and 2 p53-specific T-cell repertoire supports the rationale of using p53 long peptides in vaccination strategies aiming at the induction of p53-specific Th1/CTL immunity.
authors.affiliation: Department of Gynaecology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Annechien
authors.initials: A
authors.lastname: Lambeck
authors.forename: Ninke
authors.initials: N
authors.lastname: Leffers
authors.forename: Baukje-Nynke
authors.initials: BN
authors.lastname: Hoogeboom
authors.forename: Wim
authors.initials: W
authors.lastname: Sluiter
authors.forename: Ineke
authors.initials: I
authors.lastname: Hamming
authors.forename: Harry
authors.initials: H
authors.lastname: Klip
authors.forename: Klaske
authors.initials: K
authors.lastname: ten Hoor
authors.forename: Martha
authors.initials: M
authors.lastname: Esajas
authors.forename: Magda
authors.initials: M
authors.lastname: van Oven
authors.forename: Jan-Wouter
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Inge
authors.initials: I
authors.lastname: Platteel
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Kees
authors.initials: K
authors.lastname: Melief
authors.forename: Sjoerd
authors.initials: S
authors.lastname: van der Burg
authors.forename: Ate
authors.initials: A
authors.lastname: van der Zee
authors.forename: Toos
authors.initials: T
authors.lastname: Daemen
authors.forename: Hans
authors.initials: H
authors.lastname: Nijman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D013601:T-Lymphocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53
chemical_list: D016207:Cytokines; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1