P53-specific T cell responses in patients with malignant and benign ovarian tumors: implications for p53 based immunotherapy.
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.
Lambeck
Annechien
A
Department of Gynaecology, University Medical Center Groningen, University of Groningen, The Netherlands.
Leffers
Ninke
N
Hoogeboom
Baukje-Nynke
BN
Sluiter
Wim
W
Hamming
Ineke
I
Klip
Harry
H
ten Hoor
Klaske
K
Esajas
Martha
M
van Oven
Magda
M
Drijfhout
Jan-Wouter
JW
Platteel
Inge
I
Offringa
Rienk
R
Hollema
Harry
H
Melief
Kees
K
van der Burg
Sjoerd
S
van der Zee
Ate
A
Daemen
Toos
T
Nijman
Hans
H
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
D016207:Cytokines; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1