Increased Circulating Immunosuppressive CD14+HLA-DR-/low Cells Correlate with Clinical Cancer Stage and Pathological Grade in Patients with Bladder Carcinoma

This study investigated CD14(+)HLA-DR-/low PBMCs 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-gamma (IFN-gamma) production after addition of CD14(+)HLA-DR-/low and CD14(+)HLA-DR+ cells at different ratios were measured. IFN-gamma production was also measured after addition of L-arginine and/or antitransforming growth factor-beta (TGF-beta) 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-gamma production in a dose-dependent manner. This suppressive activity was partially reversed by L-arginine or anti-TGF-beta. Enhanced IFN-gamma 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.