title: Increased circulating immunosuppressive CD14(+)HLA-DR(-/low) cells correlate with clinical cancer stage and pathological grade in patients with bladder carcinoma.
abstract: This study investigated CD14(+)HLA-DR(-/low) cells in peripheral blood mononuclear cells (PBMCs) from 64 patients with bladder carcinoma (BC) and 14 healthy controls. Cell phenotypes were determined and CD14(+)HLA-DR(-/low) cells, CD14(+)HLA-DR(+) cells and PBMCs depleted of CD14(+)HLA-DR(-/low) cells were isolated. Proliferation of stimulated PBMCs and interferon-γ (IFN-γ) production after addition of CD14(+)HLA-DR(-/low) and CD14(+)HLA-DR(+) cells at different ratios were measured. IFN-γ production was also measured after addition of L-arginine and/or antitransforming growth factor-β (TGF-β) neutralizing monoclonal antibody, and in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The proportion of CD14(+)HLA-DR(-/low) cells in BC patients was significantly higher than in controls. CD14(+)HLA-DR(-/low) cells significantly decreased T-cell proliferation and IFN-γ production in a dose-dependent manner. This suppressive activity was partially reversed by L-arginine or anti-TGF-β. Enhanced IFN-γ secretion was also seen in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The level of CD14(+)HLA-DR(-/low) cells was associated with gender, tumour size, number of tumours, cancer pathological grade and clinical stage. CD14(+)HLA-DR(-/low) cells may represent a subpopulation of myeloid-derived suppressor cells in BC patients.
authors: Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: X-K
authors: XK
authors: Yuan
authors: X-K
authors: XK
authors: Zhao
authors: Y-C
authors: YC
authors: Xia
authors: X
authors: X
authors: Zhu
authors: P
authors: P
authors: Xiao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D001743:Urinary Bladder / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D001120:Arginine; D001119:Arginase