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THE IMPACT OF CYTOTOXIC CD* + LYMPHOCYTES REACTIVE TO PSA ON RESIDUAL DISEASE IN PATIENTS WITH PROSTATE CANCER

Dr Anthony W. Rowbottom, Dr P. E. Williams and Dr H. Kynaston

University Hospital of Wales, Cardiff

BACKGROUND: Modest work has been performed to improve the sensitivity of residual disease detection or investigate the contribution that the immune system makes in controlling metastatic tumor growth, in particular, the frequency and biological actions of peptide-specific CD8+ T lymphocytes in limiting metastatic disease and/or maintaining remission.

METHODS: Fifty three peripheral blood samples from 32 prostate cancer (PC) patients were investigated for the presence of circulating prostate-specific antigen (PSA)-expressing cells (CPECs). Using HLA-A2 tetramer complexes, frequency of CD8+ T cells specific for PSA-derived peptides was determined. Additionally, PSA and testosterone concentrations were measured in their sera.

RESULTS: CPECs were detected in 26% of peripheral blood samples from PC patients. CD8+ T cells specific for PSA-derived peptides were detected at low frequency in HLA-A2 positive PC patients. The correlation between these PSA-specific CD8+ T cells and residual prostate tumor cells and clinical measures was investigated.

CONCLUSIONS: A highly sensitive and specific assay combining immunomagnetic epithelial cell enrichment with nested RT-PCR of PSA mRNA has been optimized and characterized. Our data suggest that frequency of CD8+ T cells specific for PSA-derived peptides is correlated to circulating PSA-expressing cells, but not to serum PSA level.

Research summary dated 29 July 2005
Project 2003/12