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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3251-3257. Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2005-10-4231. This Article Full Text (PDF) All Versions of this Article: 2005-10-4231v1 107/8/3251    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 Zhou, H. Articles by Reisfeld, R. A Search for Related Content PubMed PubMed Citation Articles by Zhou, H. Articles by Reisfeld, R. A Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 25, 2005 Accepted December 7, 2005 A DNA-based cancer vaccine enhances lymphocyte crosstalk by engaging the NKG2D receptor He Zhou, Yunping Luo, Charles D Kaplan, Jorg A Kruger, Sung-Hyung Lee, Rong Xiang, and Ralph A Reisfeld* Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA * Corresponding author; email: reisfeld{at}scripps.edu. The NKG2D receptor is a stimulatory receptor expressed on NK cells and activated CD8 T cells. We previously demonstrated that engaging the NKG2D receptor markedly improved the efficacy of a survivin-based DNA vaccine. The combination vaccine encoding both the NKG2D ligand H60 and survivin activates both innate and adaptive antitumor immunity, resulting in better protection against tumors of different origin and NKG2D expression levels. Here we demonstrate that the enhanced vaccine efficacy is in part attributable to increased crosstalk between lymphocytes. Depletion of CD8 T cells during priming reduces the vaccine-induced activation of dendritic cells (DCs) and NK activity. Depletion of NK cells during priming leads to reduced DC activation and CTL activity. However, depletion of CD4 T cells results in activation of DCs, NK and CD8 T cells and enhances NK cell activity. The pH60/Survivin vaccine also increases DC and NK cells, but decreases CD4 T cells homing to Peyer's patches, presumably as a result of changes in the their homing receptor profile. Thus, by preferentially activating and attracting positive regulators, and reducing negative regulators in Peyer's patches, this dual function DNA vaccine induces a microenvironment more suitable for NK cell activation and T cell priming. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Collaboration is required for successful immunotherapy Soldano Ferrone and Eric Ko Blood 2006 107: 3025-3026. [Full Text] [PDF] This article has been cited by other articles: C. Bourquin, L. Schmidt, A.-L. Lanz, B. Storch, C. Wurzenberger, D. Anz, N. Sandholzer, R. Mocikat, M. Berger, H. Poeck, et al. Immunostimulatory RNA Oligonucleotides Induce an Effective Antitumoral NK Cell Response through the TLR7 J. Immunol., November 15, 2009; 183(10): 6078 - 6086. [Abstract] [Full Text] [PDF] W. Cao, X. Xi, Z. Wang, L. Dong, Z. Hao, L. Cui, C. Ma, and W. He Four novel ULBP splice variants are ligands for human NKG2D Int. Immunol., August 1, 2008; 20(8): 981 - 991. [Abstract] [Full Text] [PDF] W. Cao, X. Xi, Z. Hao, W. Li, Y. Kong, L. Cui, C. Ma, D. Ba, and W. He RAET1E2, a Soluble Isoform of the UL16-binding Protein RAET1E Produced by Tumor Cells, Inhibits NKG2D-mediated NK Cytotoxicity J. Biol. Chem., June 29, 2007; 282(26): 18922 - 18928. [Abstract] [Full Text] [PDF]

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