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High frequency of prostate antigen‐directed T cells in cancer patients compared to healthy age‐matched individuals
Author(s) -
Forsberg Ole,
Carlsson Björn,
Malmström PerUno,
Ullenhag Gustav,
Tötterman Thomas H.,
Essand Magnus
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20858
Subject(s) - cytotoxic t cell , antigen , cd8 , prostate cancer , epitope , ctl* , prostate specific antigen , immunology , antigen presenting cell , t cell , flow cytometry , tumor antigen , medicine , cancer research , biology , immune system , cancer , immunotherapy , in vitro , biochemistry
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)‐γ 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‐γ‐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. Prostate 69: 70–81, 2009. © 2008 Wiley–Liss, Inc.