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P53-specific T cell responses in patients with malignant and benign ovarian tumors: Implications for p53 based immunotherapy

✍ Scribed by Annechien Lambeck; Ninke Leffers; Baukje-Nynke Hoogeboom; Wim Sluiter; Ineke Hamming; Harry Klip; Klaske ten Hoor; Martha Esajas; Magda van Oven; Jan-Wouter Drijfhout; Inge Platteel; Rienk Offringa; Harry Hollema; Kees Melief; Sjoerd van der Burg; Ate van der Zee; Toos Daemen; Hans Nijman


Publisher
John Wiley and Sons
Year
2007
Tongue
French
Weight
214 KB
Volume
121
Category
Article
ISSN
0020-7136

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✦ Synopsis


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‐γ 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. © 2007 Wiley‐Liss, Inc.


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