title: Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, University Hospital Heidelberg, Heidelberg, Germany. boris.hadaschik@med.uni-heidelberg.de
authors.forename: Boris
authors.initials: B
authors.lastname: Hadaschik
authors.forename: Yun
authors.initials: Y
authors.lastname: Su
authors.forename: Eva
authors.initials: E
authors.lastname: Huter
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Ge
authors.forename: Markus
authors.initials: M
authors.lastname: Hohenfellner
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm