title: Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines.
abstract: OBJECTIVE
  Immunotherapy has faced limited success, although many solutions have been proposed. Recently regulatory T cells have made a comeback in the immunological arena and the role of these cells in patients with cancer is in focus. It is under evaluation whether the immunological status of patients with cancer may affect their sensitivity to immunotherapy. We are developing immunostimulating gene therapy for treating bladder cancer. In this study we constructed an immunological profile of patients with bladder carcinoma to understand which obstacles must be circumvented.
  
  
  METHODS
  Biopsies and blood were used to identify immune cell populations by FACS(R), histochemistry and proliferation assays, and cytokine production by polymerase chain reaction.
  
  
  RESULTS
  Results indicate that bladder carcinoma is a Tr1 dominated tumor, as shown by the infiltration of T-regulatory cells expressing FOXP3, and the presence of tumor necrosis factor-beta and interleukin-10 mRNA copies. We further noted that circulating patient T cells were unresponsive to polyclonal T-cell activation compared to healthy donor cells. Moreover, CD4+CD25+ T cells were increased in patient blood and could suppress the expansion of allogeneic T cells from healthy donors.
  
  
  CONCLUSIONS
  Patients with bladder carcinoma show an immunosuppressive regulatory profile, including nonresponsive T cells. Clinical protocols able to effectively counteract these mechanisms are warranted.
authors.affiliation: Clinical Immunology Division, Rudbeck Laboratory C11/Uppsala University, Uppsala, Sweden. angelica.loskog@klinimm.uu.se
authors.forename: Angelica
authors.initials: A
authors.lastname: Loskog
authors.forename: Christina
authors.initials: C
authors.lastname: Ninalga
authors.forename: Gabriella
authors.initials: G
authors.lastname: Paul-Wetterberg
authors.forename: Manuel
authors.initials: M
authors.lastname: de la Torre
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Tötterman
mesh_terms: D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology*
chemical_list: D008233:Lymphotoxin-alpha; D016753:Interleukin-10