Immunosuppressive CD14 + HLA‐DR low/− monocytes in prostate cancer

OBJECTIVE To determine if the levels of circulating myeloid‐derived suppressor cells increase with progression of prostate cancer (PCa); to determine if such cells could contribute to the relative inefficiency of PCa immunotherapy. MATERIALS AND METHODS We analyzed peripheral blood mononuclear cells isolated from untreated PCa patients (uPCa; N = 18; mean age ± SD: 72.1 ± 6.9 years), tPCa (N = 22; 72.8 ± 9.8 years) and age matched controls (AMC; N = 12; 68.8 ± 7.5 years). We quantified surface marker phenotype, differentiation potential, effects on T cell proliferation and intracellular cytokines. RESULTS We observed an unexpectedly high percentage of a type of myeloid‐derived suppressor cells, CD14 + HLA‐DR low/− monocytes, in tPCa (30.7 ± 15.0% of CD14 + cells) relative to AMC (4.1 ± 6.5%, P  < 0.0001) and uPCa (10.6 ± 14.3%, P  = 0.0001). The levels of CD14 + HLA‐DR low/− cells were significantly correlated with circulating PSA levels and treatment with LHRH‐agonist leuprolide in combination with either an antiandrogen or dexamethasone. Monocytes from tPCa inhibited autologous T cell proliferation statistically significantly more effectively than AMC monocytes and were defective in their ability to differentiate into phenotypically mature dendritic cells. Isolated CD14 + HLA‐DR low/− cells expressed higher levels of intracellular interleukin‐10 and suppressed T cell proliferation more effectively than isolated CD14 + HLA‐DR + cells. CONCLUSIONS This is the first report of CD14 + cells exhibiting reduced expression of HLA‐DR molecules in PCa patients. These cells suppress immune cell function in vitro and, plausibly, in vivo, a finding that must be factored into the design of immunotherapy protocols for PCa patients. Prostate 70: 443–455, 2010. © 2009 Wiley‐Liss, Inc.