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P53-specific T cell responses in patients with malignant and benign ovarian tumors: implications for p53 based
Annechien Lambeck1, Ninke Leffers, Baukje-Nynke Hoogeboom
1Department of Gynaecology, University Medical Center Groningen, University of Groningen, The Netherlands.
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.
Insights
Ovarian cancer patients show p53-specific T-cell responses in both naive and memory cells, unlike controls. This suggests p53 immunotherapy is a viable strategy for recurrent ovarian cancer.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Ovarian cancer frequently recurs despite treatment, necessitating novel therapeutic strategies like immunotherapy.
- The p53 protein, often overexpressed in ovarian cancer, presents a potential target for immune-based therapies.
Purpose of the Study:
- To investigate the characteristics and extent of the pre-existing immune response against p53 in ovarian cancer patients.
- To determine if p53-specific T-cell responses differ between ovarian cancer patients and healthy/benign controls.
Main Methods:
- Analysis of T-cell responses targeting the p53 protein in ovarian cancer patients and control groups.
- Characterization of T-cell subsets (naïve vs. memory) and cytokine profiles (IFN-gamma, IL-4, IL-5, IL-10).
- Detection of p53-specific T cells in peripheral blood, tumor tissue, and lymph nodes.
Main Results:
- P53-specific T-cell responses were found in both ovarian cancer patients and controls.
- Ovarian cancer patients exhibited p53-specific T-cell responses in both naïve (CD45RA+) and memory (CD45RO+) T-cell subsets, unlike controls who only showed responses in naïve cells.
- These memory T-cell responses produced a mix of type 1 (IFN-gamma) and type 2 (IL-4, IL-5) cytokines, along with IL-10.
- P53-specific T cells were identified in peripheral blood, tumor-infiltrating lymphocytes, and tumor-draining lymph nodes.
Conclusions:
- The presence of p53-specific memory T cells in ovarian cancer patients indicates successful antigen presentation and immune priming.
- A weak, mixed T-helper type 1 and 2 immune response against p53 was observed.
- These findings support the use of p53 long peptides in vaccination strategies to induce robust p53-specific T-helper type 1/cytotoxic T-lymphocyte immunity for ovarian cancer treatment.
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