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Blood, 27 August 2009, Vol. 114, No. 9, pp. 1776-1783. Prepublished online as a Blood First Edition Paper on June 26, 2009; DOI 10.1182/blood-2008-12-192419. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-12-192419v1 114/9/1776    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 Klebanoff, C. A. Articles by Restifo, N. P. PubMed PubMed Citation Articles by Klebanoff, C. A. Articles by Restifo, N. P. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccination Christopher A. Klebanoff1,2,*, Zhiya Yu2,*, Leroy N. Hwang2, Douglas C. Palmer2, Luca Gattinoni2, and Nicholas P. Restifo2 1 Howard Hughes Medical Institute–National Institutes of Health Research Scholars Program, Bethesda, MD; and 2 Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD Naive and memory CD8+ T cells can undergo programmed activation and expansion in response to a short T-cell receptor stimulus, but the extent to which in vitro programming can qualitatively substitute for an in vivo antigen stimulation remains unknown. We show that self-/tumor-reactive effector memory CD8+ T cells (TEM) programmed in vitro either with peptide-pulsed antigen-presenting cells or plate-bound anti-CD3/anti-CD28 embark on a highly stereotyped response of in vivo clonal expansion and tumor destruction nearly identical to that of vaccine-stimulated TEM cells. This programmed response was associated with an interval of antigen-independent interferon- (IFN-) release that facilitated the dynamic expression of the major histocompatibility complex class I restriction element H-2Db on responding tumor cells, leading to recognition and subsequent tumor lysis. Delaying cell transfer for more than 24 hours after stimulation or infusion of cells deficient in IFN- entirely abrogated the benefit of the programmed response, whereas transfer of cells unable to respond to IFN- had no detriment to antitumor immunity. These findings extend the phenomenon of a programmable effector response to memory CD8+ T cells and have major implications for the design of current adoptive-cell transfer trials. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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