Differential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer.
Affiliation
Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK. eelkord@picr.man.ac.ukIssue Date
2005-10
Metadata
Show full item recordAbstract
Induction of CTL responses specific for prostate-specific antigen (PSA)-derived peptides in healthy individuals and patients with prostate cancer (PC) was investigated. Eight PSA-derived peptides that have the potential to bind HLA-A2 molecules were examined. Peripheral blood lymphocytes isolated from HLA-A2-positive volunteers were expanded using autologous mature, PSA-derived peptide-pulsed dendritic cells. The expansion of IFN-gamma-secreting CD8+ T cells specific for three of the eight PSA-derived peptides (PSA-2(108-117), PSA-4(141-150) and PSA-6(146-154)) was detected in healthy individuals, but not in patients with PC. Using HLA-A2/peptide tetramers, the PSA-specific CD8+ T cells were detectable at low frequency both in healthy individuals and patients with PC. Using flow cytometric cytotoxicity assays, the expanded effectors from healthy individuals were able to kill the PSA-expressing epithelial cell line LNCaP and the peptide-pulsed T2 cells in a MHC class I-restricted manner without involving NK activity. However, such killing by effectors expanded from prostatectomized patients involved a complete or a significant NK activity. Specific recognition of PSA-derived peptides in healthy individuals may occur by an adaptive CTL immune response, while such recognition in PC patients may additionally or alternatively be mediated by an innate NK immune response. In conclusion, our work indicates that the PSA-specific CD8+ T cells exist in both healthy individuals and PC patients, but they have impaired function in patients as they failed to release IFN-gamma and to kill targets without involving NK activity.Citation
Differential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer. 2005, 17 (10):1315-25 Int. Immunol.Journal
International ImmunologyDOI
10.1093/intimm/dxh309PubMed ID
16141246Type
ArticleLanguage
enISSN
0953-8178ae974a485f413a2113503eed53cd6c53
10.1093/intimm/dxh309
Scopus Count
Collections
Related articles
- High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals.
- Authors: Forsberg O, Carlsson B, Malmström PU, Ullenhag G, Tötterman TH, Essand M
- Issue date: 2009 Jan 1
- Induction of human tumor-associated differentially expressed gene-12 (TADG-12/TMPRSS3)-specific cytotoxic T lymphocytes in human lymphocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer.
- Authors: Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD
- Issue date: 2009 Feb 15
- Correlation between CD8+ T cells specific for prostate-specific antigen and level of disease in patients with prostate cancer.
- Authors: Elkord E, Rowbottom AW, Kynaston H, Williams PE
- Issue date: 2006 Jul
- A parathyroid-hormone-related-protein (PTH-rP)-specific cytotoxic T cell response induced by in vitro stimulation of tumour-infiltrating lymphocytes derived from prostate cancer metastases, with epitope peptide-loaded autologous dendritic cells and low-dose IL-2.
- Authors: Correale P, Micheli L, Vecchio MT, Sabatino M, Petrioli R, Pozzessere D, Marsili S, Giorgi G, Lozzi L, Neri P, Francini G
- Issue date: 2001 Nov 30
- Generation of human cytolytic T lymphocyte lines directed against prostate-specific antigen (PSA) employing a PSA oligoepitope peptide.
- Authors: Correale P, Walmsley K, Zaremba S, Zhu M, Schlom J, Tsang KY
- Issue date: 1998 Sep 15