Is the spontaneous anti-tumor T cell response of breast carcinoma patients a clinical prognostic factor ?


Several retrospective studies suggest a correlation between the survival of patients with ovarian or colorectal carcinoma and infiltration of their tumors by immune cells. So far, prospective data validating these observations do not exist. In collaboration with Dr Javier Carrasco (Grand Hôpital de Charleroi) and Dr Jean-Pascal Machiels (Cliniques Universitaires St-Luc), we set out a prospective study aimed at looking for a correlation between the clinical outcome of patients with non-metastatic breast carcinoma and their spontaneous anti-tumor T cell response.
Considering our experience in quantitative approaches to detect very weak T cell responses in the blood of melanoma patients, Danièle Godelaine set out the evaluation of the frequencies of anti-tumor CD8 T lymphocytes in the blood of breast cancer patients recruited in the two clinical centers.
Frequencies are evaluated by mixed lymphocyte-peptide cultures, carried out with HLA-A2 and A3-restricted peptides derived from HER2/neu and hTERT, two proteins usually overexpressed in breast tumors, followed by detection of specific cells with HLA-peptide tetramers. Blood samples are collected before and after surgery. Tumors removed at surgery are analyzed by immunohistology for infiltration by immune cells, and fragments are frozen for further analysis.
This prospective study foresees to include 172 patients whose clinical evolution will be followed up over a 5-year period. So far, 25 patients have been included. Eight of them have a frequency against the targeted antigens ranging from 10-5 and 10-6 among blood CD8 T cells, whereas the frequency in healthy donors blood was estimated to be lower than 5x10-7.
We hope to identify the patients with a better prognosis in order to offer them an adapted care avoiding unnecessary heavy treatments.



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