title: Increase of regulatory T cells in the peripheral blood of cancer patients.
abstract: OBJECTIVE
  T cells constitutively expressing both CD4 and CD25are essential for maintenance of self-tolerance and therefore have been referred to as regulatory T cells (Treg). Experimental tumor models in mice revealed that Tregs are potent inhibitors of an antitumor immune response. The current study was designed to determine whether cancer patients exhibit an expanded Treg pool.
  
  
  METHODS
  The frequency of Tregs in the peripheral blood of 42 patients suffering from epithelial malignancies and from 34 healthy controls was determined by flow cytometry. The immunoregulatory properties of CD4(+)CD25(+) and CD4(+)CD25(-) T cells were characterized by proliferation and suppression assays. Cocultures with natural killer (NK) cells were performed to determine the impact of Tregs on NK-mediated cytotoxicity.
  
  
  RESULTS
  Patients with epithelial malignancies show an increase of CD4(+)CD25(+) T cells in the peripheral blood with characteristics of Tregs, i.e., they are CD45RA(-), CTLA-4(+), and transforming growth factor beta(+). Notably, CD4(+) T cells from cancer patients are characterized by an impaired proliferative capacity, which is restored to the extend of CD25-depleted CD4(+) T cells from control persons by prior removal of CD25(+) T cells. In contrast to CD4(+)CD25(-) T cells, isolated CD4(+)CD25(+) T cells from cancer patients were anergic towards T cell receptor stimulation. In addition, CD4(+)CD25(+) T cells suppressed the proliferation of CD4(+)CD25(-) T cells. When cultured together with CD56(+) NK-cells, CD4(+)CD25(+) T cells from cancer patients effectively inhibited NK-cell-mediated cytotoxicity.
  
  
  CONCLUSIONS
  Thus, we provide evidence of an increased pool of CD4(+)CD25(+) regulatory T cells in the peripheral blood of cancer patients with potent immunosuppressive features. These findings should be considered for the design of immunomodulatory therapies such as dendritic cell vaccination.
authors.affiliation: Institute for Biomedical Aging Research, Austrian Academy of Sciences, 6020 Innsbruck, Austria. Maria.Wolf@oeaw.ac.at
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Wolf
authors.forename: Dominik
authors.initials: D
authors.lastname: Wolf
authors.forename: Michael
authors.initials: M
authors.lastname: Steurer
authors.forename: Guenther
authors.initials: G
authors.lastname: Gastl
authors.forename: Eberhard
authors.initials: E
authors.lastname: Gunsilius
authors.forename: Beatrix
authors.initials: B
authors.lastname: Grubeck-Loebenstein
mesh_terms: D015703:Antigens, CD / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005833:Genital Neoplasms, Female / Q000097:blood / Q000276:immunology / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D009367:Neoplasm Staging; D009369:Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D012016:Reference Values; D013274:Stomach Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD