High frequency of prostate antigen-directed T cells in cancer patients compared to healthy age-matched individuals.
BACKGROUND
In order to obtain a sustained cytotoxic T lymphocyte (CTL) response against cancer cells it is preferable to have CTLs directed against multiple peptide epitopes from numerous tumor-associated antigens.


METHODS
We used a Flow Cytometry-based interferon (IFN)-gamma secretion assay with peptide-pulsed C1R-A2 as antigen-presenting cells to analyze whether CD8+ T cells directed against any of 24 HLA-A*0201-binding peptides from 15 prostate-associated proteins can be found in the peripheral blood of patients with localized prostate cancer. We also investigated whether multiple prostate antigen-specific CD8+ T cells can be generated simultaneously, from a naïve T cell repertoire. In that case, dendritic cells (DCs) from peripheral blood of healthy donors were divided in six portions and separately pulsed with six peptides. The peptide-pulsed DCs were then pooled and used to stimulate autologous T cells. The T cells were re-stimulated with peptide-pulsed monocytes.


RESULTS
We found prostate antigen-restricted CD8+ T cells in the peripheral blood in 48 out of 184 (26.1%) analyzed samples from 25 cancer patients. This is significantly higher than 17 out of 214 analyzed samples (7.9%) from 10 healthy age-matched male individuals (P = 0.0249). In the cases when antigen-specific T cells could not be detected, we were able to generate IFN-gamma-producing CD8+ T cells specific for up to three prostate antigens simultaneously from a naïve T cell repertoire.


CONCLUSIONS
CD8+ T cells directed against prostate antigen peptides can be found in, or generated from, peripheral blood. This indicates that such T cells could be expanded ex vivo for adoptive transfer to prostate cancer patients.
Forsberg
Ole
O
Clinical Immunology Division, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Carlsson
Björn
B
Malmström
Per-Uno
PU
Ullenhag
Gustav
G
Tötterman
Thomas H
TH
Essand
Magnus
M
D019264:Adoptive Transfer; D000367:Age Factors; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000276:immunology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007371:Interferon-gamma