title: Circulating immunosuppressive cells of prostate cancer patients before and after radical prostatectomy: profile comparison.
abstract: OBJECTIVE
  A dendritic cell-based cancer vaccine has recently received Food and Drug Administration approval in the USA based on its ability to prolong the survival of prostate cancer patients with advanced disease. However, tumor-mediated immunosuppressive mechanisms might represent an obstacle to optimal performance of this therapy. We have recently shown that monocytes from the blood of prostate cancer patients can fully mature to dendritic cells only after the tumor is removed. Here, we have tested the hypothesis that these tumor-driven monocytes correspond to the recently described subset of CD14(+) HLA-DR(low) immunosuppressor cells.
  
  
  METHODS
  Prostate cancer patients were studied before and 1 month after prostatectomy. Pre- and postsurgical patients with colorectal cancer were also included for comparison. Flow cytometric analysis was applied to define CD14(-) HLA-DR(low) CD33(+) CD11b(+) (myeloid) and CD14(+) HLA-DR(low) (monocytic) suppressor cells. Interferon-γ release was used to assess the immunocompetence of lymphocytes.
  
  
  RESULTS
  In both prostate cancer and colorectal cancer patients, the percentage of CD14(+) HLA-DR(low) cells was several-fold higher compared with normal subjects. This was not the case for CD14(-) HLA-DR(low) CD33(+) CD11b(+) cells. Furthermore, postsurgical normalization of CD14(+) HLA-DR(low) cells only occurred in prostate cancer patients. In all patients, the interferon-γ response of T lymphocytes to phorbolmyristate acetate-ionomycin was higher compared with normal donors, but it was further increased after tumor ablation only in prostate cancer patients.
  
  
  CONCLUSIONS
  The direct link between CD14(+) HLA-DR(low) increase and presence of primary tumor suggests a distinguishing immunosuppressive profile of prostate cancer. This observation supports the principle that the appropriate setting for prostate cancer vaccine therapy is a minimal disease status.
authors: Laboratory of Tumor Immunology, University of Turin, Turin, Italy; Department of Internal Medicine, University of Turin, Turin, Italy.
authors: Davide
authors: D
authors: Brusa
authors: Mariagrazia
authors: M
authors: Simone
authors: Paolo
authors: P
authors: Gontero
authors: Rosella
authors: R
authors: Spadi
authors: Patrizia
authors: P
authors: Racca
authors: Jasmin
authors: J
authors: Micari
authors: Maurizio
authors: M
authors: Degiuli
authors: Sara
authors: S
authors: Carletto
authors: Alessandro
authors: A
authors: Tizzani
authors: Lina
authors: L
authors: Matera
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D039481:CD11b Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007121:Immunocompetence / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; C571163:CD33 protein, human; D019496:Cancer Vaccines; D006684:HLA-DR Antigens; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D063268:Sialic Acid Binding Ig-like Lectin 3
keywords: colorectal cancer; dendritic cells; myeloid derived suppressor cells; prostate cancer; vaccine therapy