Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines.
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.
Loskog
Angelica
A
Clinical Immunology Division, Rudbeck Laboratory C11/Uppsala University, Uppsala, Sweden. angelica.loskog@klinimm.uu.se
Ninalga
Christina
C
Paul-Wetterberg
Gabriella
G
de la Torre
Manuel
M
Malmström
Per-Uno
PU
Tötterman
Thomas H
TH
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*
D008233:Lymphotoxin-alpha; D016753:Interleukin-10