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Blood, 29 October 2009, Vol. 114, No. 18, pp. 3793-3802. Prepublished online as a Blood First Edition Paper on September 1, 2009; DOI 10.1182/blood-2009-03-208181. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-03-208181v1 114/18/3793    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 CrossRef Google Scholar Articles by Zhou, Q. Articles by Blazar, B. R. PubMed PubMed Citation Articles by Zhou, Q. Articles by Blazar, B. R. Related Collections Immunobiology Transplantation Myeloid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia Qing Zhou1, Christoph Bucher1, Meghan E. Munger1, Steven L. Highfill1, Jakub Tolar1, David H. Munn2, Bruce L. Levine3, Megan Riddle1, Carl H. June3, Daniel A. Vallera4, Brenda J. Weigel1, and Bruce R. Blazar1 1 Department of Pediatrics, Division of Blood and Marrow Transplantation, Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis; 2 Department of Pediatrics, School of Medicine, Medical College of Georgia, Augusta; 3 Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia; and 4 Department of Therapeutic Radiology, Masonic Cancer Center, University of Minnesota, Twin Cities, Minneapolis Tumor-induced immune suppression can permit tumor cells to escape host immune resistance. To elucidate host factors contributing to the poor response of adoptively transferred tumor-reactive cytotoxic T lymphocytes (CTLs), we used a systemic model of murine acute myeloid leukemia (AML). AML progression resulted in a progressive regulatory T-cell (Treg) accumulation in disease sites. The adoptive transfer of in vitro–generated, potently lytic anti–AML-reactive CTLs failed to reduce disease burden or extend survival. Compared with non–AML-bearing hosts, transferred CTLs had reduced proliferation in AML sites of metastases. Treg depletion by a brief course of interleukin-2 diphtheria toxin (IL-2DT) transiently reduced AML disease burden but did not permit long-term survival. In contrast, IL-2DT prevented anti-AML CTL hypoproliferation, increased the number of transferred CTLs at AML disease sites, reduced AML tumor burden, and resulted in long-term survivors that sustained an anti-AML memory response. These data demonstrated that Tregs present at AML disease sites suppress adoptively transferred CTL proliferation, limiting their in vivo expansion, and Treg depletion before CTL transfer can result in therapeutic efficacy in settings of substantial pre-existing tumor burden in which antitumor reactive CTL infusion alone has proven ineffective. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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