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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4810-4815. Prepublished online as a Blood First Edition Paper on February 20, 2007; DOI 10.1182/blood-2006-11-057216. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-11-057216v1 109/11/4810    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 French, R. R. Articles by Glennie, M. J. Search for Related Content PubMed PubMed Citation Articles by French, R. R. Articles by Glennie, M. J. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Eradication of lymphoma by CD8 T cells following anti-CD40 monoclonal antibody therapy is critically dependent on CD27 costimulation Ruth R. French1, Vadim Y. Taraban1, Graham R. Crowther1, Tania F. Rowley1, Juliet C. Gray1, Peter W. Johnson1, Alison L. Tutt1, Aymen Al-Shamkhani1, and Martin J. Glennie1 1 Tenovus Research Laboratory, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton, United Kingdom Growing evidence points to the potential of agonistic anti-CD40 mAbs as adjuvants for vaccination against cancer. These appear to act by maturing dendritic cells (DCs) and allowing them to prime CD8 cytotoxic T lymphocytes (CTLs). Although it is well established that optimal T-cell priming requires costimulation via B7:CD28, recent studies emphasize the contribution of TNF receptors to this process. To understand how anti-CD40 mAbs trigger effective antitumor immunity, we investigated the role of TNFR superfamily members CD27 and 4-1BB in the generation of this immunity and showed that, although partially dependent on 4-1BB:4-1BBL engagement, it is completely reliant on CD27:CD70 interactions. Importantly, blocking CD70, and to some extent 4-1BBL, during anti-CD40 treatment prevented accumulation of tumor-reactive T cells and subsequent tumor protection. However, it did not influence changes in DC number, phenotype, nor the activity of CTLs once immunity was established. We conclude that CD27:CD70 and 4-1BB:4-1BBL interactions are needed for DC-driven accumulation of antitumor CTLs following anti-CD40 mAb treatment. Finally, in support of the critical role for CD70:CD27, we show for the first time that agonistic anti-CD27 mAbs given without a DC maturation signal completely protect tumor-bearing mice and provide a highly potent reagent for boosting antitumor T-cell immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Hashimoto-Okada, T. Kitawaki, N. Kadowaki, S. Iwata, C. Morimoto, T. Hori, and T. Uchiyama The CD70-CD27 interaction during the stimulation with dendritic cells promotes naive CD4+ T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humans Int. Immunol., June 25, 2009; (2009) dxp056v1. [Abstract] [Full Text] [PDF] B. Zhao, A. Song, R. Haque, F. Lei, L. Weiler, X. Xiong, Y. Wu, M. Croft, and J. Song Cooperation between Molecular Targets of Costimulation in Promoting T Cell Persistence and Tumor Regression J. Immunol., June 1, 2009; 182(11): 6744 - 6752. [Abstract] [Full Text] [PDF] A. M. Keller, Y. Xiao, V. Peperzak, S. H. Naik, and J. Borst Costimulatory ligand CD70 allows induction of CD8+ T-cell immunity by immature dendritic cells in a vaccination setting Blood, May 21, 2009; 113(21): 5167 - 5175. [Abstract] [Full Text] [PDF] M. Zhang, Z. Yao, S. Dubois, W. Ju, J. R. Muller, and T. A. Waldmann Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer PNAS, May 5, 2009; 106(18): 7513 - 7518. [Abstract] [Full Text] [PDF] K. P. J. M. van Gisbergen, R. W. van Olffen, J. van Beek, K. F. van der Sluijs, R. Arens, M. A. Nolte, and R. A. van Lier Protective CD8 T Cell Memory Is Impaired during Chronic CD70-Driven Costimulation J. Immunol., May 1, 2009; 182(9): 5352 - 5362. [Abstract] [Full Text] [PDF] C. F. Skibola, A. Nieters, P. M. Bracci, J. D. Curry, L. Agana, D. R. Skibola, A. Hubbard, N. Becker, M. T. Smith, and E. A. Holly A functional TNFRSF5 gene variant is associated with risk of lymphoma Blood, April 15, 2008; 111(8): 4348 - 4354. [Abstract] [Full Text] [PDF] V. Y. Taraban, S. Martin, K. E. Attfield, M. J. Glennie, T. Elliott, D. Elewaut, S. Van Calenbergh, B. Linclau, and A. Al-Shamkhani Invariant NKT Cells Promote CD8+ Cytotoxic T Cell Responses by Inducing CD70 Expression on Dendritic Cells J. Immunol., April 1, 2008; 180(7): 4615 - 4620. [Abstract] [Full Text] [PDF] A. Kretz-Rommel, F. Qin, N. Dakappagari, R. Cofiell, S. J. Faas, and K. S. Bowdish Blockade of CD200 in the Presence or Absence of Antibody Effector Function: Implications for Anti-CD200 Therapy J. Immunol., January 15, 2008; 180(2): 699 - 705. [Abstract] [Full Text] [PDF]

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