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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 15, 2005 Accepted May 15, 2005 Reduced frequencies and suppressive function of CD4+ CD25high 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* Molecular Tumor Biology and Tumor Immunology, University of Cologne, Cologne, Germany; Clinic I for Internal Medicine, University of Cologne, Cologne, Germany Institute for Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany Clinic I for Internal Medicine, University of Cologne, Cologne, Germany * Corresponding author; email: joachim.schultze{at}uk-koeln.de. Globally suppressed T cell function has been described in many cancer patients to be a major hurdle for the development of clinically efficient cancer immunotherapy. Inhibition of anti-tumor immune responses has been mainly linked to inhibitory factors present in cancer patients. More recently, increased frequencies of CD4+ CD25high regulatory T cells (Treg cells) have been described as an additional mechanism reducing immunity. Assessing 73 B cell chronic lymphocytic leukemia (CLL) patients and 42 healthy controls we demonstrate significantly increased frequencies of CTLA4+ FOXP3+ GITR+ CD62L+ TGF1+ IL-10+ Treg cells in CLL patients, with highest frequencies in untreated or progressing patients presenting with extended disease. Most surprisingly, in the majority of CLL patients 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 immune suppression 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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