Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer

Stanimir Vuk-Pavlović, Peggy A. Bulur, Yi Lin, Rui Qin, Carol L. Szumlanski, Xinghua Zhao, Allan B. Dietz

Research output: Contribution to journalArticlepeer-review

187 Scopus citations

Abstract

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-DRlow/- 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 HLADRmolecules 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.

Original languageEnglish (US)
Pages (from-to)443-455
Number of pages13
JournalProstate
Volume70
Issue number4
DOIs
StatePublished - Mar 1 2010

Keywords

  • Androgen suppression
  • CD14 cells
  • Dendritic cells
  • HLA-DR expression
  • Monocytes
  • Myeloid-derived suppressor cells
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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