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 journalArticle

175 Citations (Scopus)

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

Fingerprint

Immunosuppressive Agents
Monocytes
Prostatic Neoplasms
HLA-DR Antigens
Cell Proliferation
T-Lymphocytes
Immunotherapy
Leuprolide
Androgen Antagonists
Differentiation Antigens
Gonadotropin-Releasing Hormone
Interleukin-10
Dendritic Cells
Dexamethasone
Blood Cells
Cytokines
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Vuk-Pavlović, S., Bulur, P. A., Lin, Y., Qin, R., Szumlanski, C. L., Zhao, X., & Dietz, A. B. (2010). Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer. Prostate, 70(4), 443-455. https://doi.org/10.1002/pros.21078

Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer. / Vuk-Pavlović, Stanimir; Bulur, Peggy A.; Lin, Yi; Qin, Rui; Szumlanski, Carol L.; Zhao, Xinghua; Dietz, Allan B.

In: Prostate, Vol. 70, No. 4, 01.03.2010, p. 443-455.

Research output: Contribution to journalArticle

Vuk-Pavlović, S, Bulur, PA, Lin, Y, Qin, R, Szumlanski, CL, Zhao, X & Dietz, AB 2010, 'Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer', Prostate, vol. 70, no. 4, pp. 443-455. https://doi.org/10.1002/pros.21078
Vuk-Pavlović S, Bulur PA, Lin Y, Qin R, Szumlanski CL, Zhao X et al. Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer. Prostate. 2010 Mar 1;70(4):443-455. https://doi.org/10.1002/pros.21078
Vuk-Pavlović, Stanimir ; Bulur, Peggy A. ; Lin, Yi ; Qin, Rui ; Szumlanski, Carol L. ; Zhao, Xinghua ; Dietz, Allan B. / Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer. In: Prostate. 2010 ; Vol. 70, No. 4. pp. 443-455.
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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.",
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T1 - Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer

AU - Vuk-Pavlović, Stanimir

AU - Bulur, Peggy A.

AU - Lin, Yi

AU - Qin, Rui

AU - Szumlanski, Carol L.

AU - Zhao, Xinghua

AU - Dietz, Allan B

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N2 - 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.

AB - 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.

KW - Androgen suppression

KW - CD14 cells

KW - Dendritic cells

KW - HLA-DR expression

KW - Monocytes

KW - Myeloid-derived suppressor cells

KW - Prostate cancer

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