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Human bladder carcinoma is dominated by T-regulatory cells and Th1 inhibitory cytokines
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2007 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 177, no 1, 353-358 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: 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. Materials and Methods: Biopsies and blood were used to identify immune cell populations by FACS®, histochemistry and proliferation assays, and cytokine production by polymerase chain reaction. Results: Results indicate that bladder carcinoma is a Tri dominated tumor, as shown by the infiltration of T-regulatory cells expressing FOXP3, and the presence of tumor necrosis factor-β 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.

Place, publisher, year, edition, pages
2007. Vol. 177, no 1, 353-358 p.
Keyword [en]
bladder, bladder neoplasms, FOXP3 protein, human, immune tolerance, regulatory, T-lymphocytes
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-16807DOI: 10.1016/j.juro.2006.08.078ISI: 000242843200102PubMedID: 17162090OAI: oai:DiVA.org:uu-16807DiVA: diva2:44578
Available from: 2008-06-05 Created: 2008-06-05 Last updated: 2017-12-08Bibliographically approved

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Loskog, Angelicade la Torre, ManuelMalmström, Per-UnoTötterman, Thomas H.

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