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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2018-2025.
Prepublished online as a Blood First Edition Paper on May 24, 2005; DOI 10.1182/blood-2005-02-0642.
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IMMUNOBIOLOGY
Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine
Marc Beyer,
Matthias Kochanek,
Kamruz Darabi,
Alexey Popov,
Markus Jensen,
Elmar Endl,
Percy A. Knolle,
Roman K. Thomas,
Michael von Bergwelt-Baildon,
Svenja Debey,
Michael Hallek, and
Joachim L. Schultze
From the Molecular Tumor Biology and Tumor Immunology, University of Cologne, Cologne, Germany; Clinic I for Internal Medicine, University of Cologne, Cologne, Germany; and Institute for Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany.
Globally suppressed T-cell function has been described in many patients with cancer to be a major hurdle for the development of clinically efficient cancer immunotherapy. Inhibition of antitumor immune responses has been mainly linked to inhibitory factors present in cancer patients. More recently, increased frequencies of CD4+CD25hi regulatory T cells (Treg cells) have been described as an additional mechanism reducing immunity. We assessed 73 patients with B-cell chronic lymphocytic leukemia (CLL) and 42 healthy controls and demonstrated significantly increased frequencies of cytotoxic T lymphocyte-associated protein 4 (CTLA4+), Forkhead box P3 (FOXP3+), glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR+), CD62L+, transforming growth factor 1 (TGF- 1+), interleukin 10 (IL-10+)Treg cells in patients with CLL, with highest frequencies in untreated or progressing patients presenting with extended disease. Most surprisingly, in the majority of patients with CLL treated with fludarabine-containing therapy regimens the inhibitory function of Treg cells was decreased or even abrogated. In addition, frequencies of Treg cells were significantly decreased after therapy with fludarabine. In light of similar findings for cyclophosphamide the combination of fludarabine and cyclophosphamide might be further exploited in strategies reducing immunosuppression prior to cancer immunotherapy.

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