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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. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-02-0642v1 106/6/2018    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Beyer, M. Articles by Schultze, J. L. Search for Related Content PubMed PubMed Citation Articles by Beyer, M. Articles by Schultze, J. L. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF] L. Zhang, T. F. Gajewski, and J. Kline PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model Blood, August 20, 2009; 114(8): 1545 - 1552. [Abstract] [Full Text] [PDF] P. B. Olkhanud, D. Baatar, M. Bodogai, F. Hakim, R. Gress, R. L. Anderson, J. Deng, M. Xu, S. Briest, and A. 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