Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer

Purpose - Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. - Materials and Methods - Peripher...

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Main Authors: Hadaschik, Boris (Author) , Su, Yun (Author) , Hüter, Eva (Author) , Ge, Yingzi (Author) , Hohenfellner, Markus (Author) , Beckhove, Philipp (Author)
Format: Article (Journal)
Language:English
Published: April 2012
In: The journal of urology
Year: 2012, Volume: 187, Issue: 4, Pages: 1458-1465
ISSN:1527-3792
DOI:10.1016/j.juro.2011.11.083
Online Access:Verlag, Volltext: http://dx.doi.org/10.1016/j.juro.2011.11.083
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0022534711057405
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Author Notes:Boris Hadaschik, Yun Su, Eva Huter, Yingzi Ge, Markus Hohenfellner and Philipp Beckhove
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Summary:Purpose - Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. - Materials and Methods - Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. - Results - In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. - Conclusions - Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells.
Item Description:Available online 16 February 2012
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Physical Description:Online Resource
ISSN:1527-3792
DOI:10.1016/j.juro.2011.11.083