Original Article: Clinical Investigation Circulating immunosuppressive cells of prostate cancer patients before and after radical prostatectomy: Profile comparison Davide Brusa, 1,4 Mariagrazia Simone, 1,4 Paolo Gontero, 2 Rosella Spadi, 3 Patrizia Racca, 3 Jasmin Micari, 3 Maurizio Degiuli, 3 Sara Carletto, 1,4 Alessandro Tizzani 2 and Lina Matera 1,4 1 Laboratory of Tumor Immunology, University ofTurin, Turin, Italy, 2 Urology Department, and 3 Colorectal Cancer Unit, Oncology and Hematology Department, San Giovanni Battista Hospital, University ofTurin, Turin, Italy, and 4 Department of Internal Medicine, University of Turin, Turin, Italy Abbreviations & Acronyms CRC = colorectal cancer CTL = cytotoxic T lymphocytes DC = dendritic cells IFN = interferon mDC = myeloid dendritic cells MDSC = myeloid-derived suppressor cells PBMC = peripheral blood mononuclear cells PCa = prostate cancer pDC = plasmocytoid dendritic cells PHA = phytohemagglutinin PMA = phorbolmyristate acetate PSA = prostate-specific antigen PSMA = prostate-specific membrane antigen Tregs = regulatory T cells Correspondence: Lina Matera Ph.D., Department of Internal Medicine, University of Turin, Corso Dogliotti, 14, Turin 10126, Italy. Email: lina.matera@unito.it Received 7 August 2012; accepted 20 December 2012. Online publication 20 February 2013 Objectives: 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 immunosup- pressive 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 prostate- ctomy. 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-g 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 normali- zation of CD14 + HLA-DR low cells only occurred in prostate cancer patients. In all patients, the interferon-g 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. Key words: colorectal cancer, dendritic cells, myeloid derived suppressor cells, pros- tate cancer, vaccine therapy. Introduction DC are key players of the adaptive T cell immunity. Their ability to cross-present tumor antigens has been exploited in clinical trails based on the administration of ex vivo generated autologous DC. 1–3 Recently, a DC-based cancer vaccine has been licensed because of its ability to increase survival of PCa patients with asymptomatic or minimally symptomatic metastatic castration-resistant PCa. 4 An obstacle to optimal performance of this therapy is the presence of the tumor.Tumor-mediated immunosuppressive mechanisms 5,6 can in fact impair both the quality of the DC vaccines, generated ex vivo from patients’ blood DC precursors, and the ability of patients’ T cells to mount an effective antitumor response in vivo. The most important cells the tumor uses to accomplish immunoescape are Tregs and MDSC. Tregs, which play a homeostatic role on the physiology of the immune response, are International Journal of Urology (2013) 20, 971–978 doi: 10.1111/iju.12086 © 2013 The Japanese Urological Association 971