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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2465-2472. Prepublished online as a Blood First Edition Paper on November 16, 2004; DOI 10.1182/blood-2004-08-3105. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3105v1 105/6/2465    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 Schnurr, M. Articles by Cebon, J. Search for Related Content PubMed PubMed Citation Articles by Schnurr, M. Articles by Cebon, J. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery Max Schnurr, Qiyuan Chen, Amanda Shin, Weisan Chen, Tracey Toy, Corinna Jenderek, Simon Green, Lena Miloradovic, Debbie Drane, Ian D. Davis, Jose Villadangos, Ken Shortman, Eugene Maraskovsky, and Jonathan Cebon From the Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria, Australia; and CSL Limited and the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. Dendritic cells (DCs) are being evaluated for cancer immunotherapy due to their unique ability to induce tumor-directed T-cell responses. Here we report that the type of human DC, the mode of activation, and the strategy for delivery of antigen are 3 critical factors for efficient stimulation of tumor-specific CD8+ and CD4+ T cells. Only CD1c+ blood DCs and monocyte-derived DCs (MoDCs) were capable of presenting epitopes of the full-length tumor antigen NY-ESO-1 on both major histocompatibility complex (MHC) class I (cross-presentation) and MHC II, whereas plasmacytoid DCs were limited to MHC II presentation. Cross-presentation was inefficient for soluble protein, but highly efficient for antigen-antibody immune complexes (NY-ESO-1/IC) and for protein formulated with ISCOMATRIX adjuvant (NY-ESO-1/IMX). DC activation with CD40L further enhanced cross-presentation efficiency. The mode of antigen delivery was found to be a determining factor for cytosolic proteolysis by DCs. Immune complexes (ICs) targeted a slow, proteasome-dependent cross-presentation pathway, whereas ISCOMATRIX (IMX) targeted a fast, proteasome-independent pathway. Both cross-presentation pathways resulted in a long-lived, T-cell stimulatory capacity, which was maintained for several days longer than for DCs pulsed with peptide. This may provide DCs with ample opportunities for sensitizing tumor-specific T cells against a broad array of tumor antigen epitopes in lymph nodes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Verdijk, E. H.J.G. Aarntzen, W. J. Lesterhuis, A.C. I. Boullart, E. Kok, M. M. van Rossum, S. Strijk, F. Eijckeler, J. J. Bonenkamp, J. F.M. Jacobs, et al. Limited Amounts of Dendritic Cells Migrate into the T-Cell Area of Lymph Nodes but Have High Immune Activating Potential in Melanoma Patients Clin. Cancer Res., April 1, 2009; 15(7): 2531 - 2540. [Abstract] [Full Text] [PDF] T. Nicholaou, L. M. Ebert, I. D. Davis, G. A. McArthur, H. Jackson, N. Dimopoulos, B. Tan, E. Maraskovsky, L. Miloradovic, W. Hopkins, et al. Regulatory T-Cell-Mediated Attenuation of T-Cell Responses to the NY-ESO-1 ISCOMATRIX Vaccine in Patients with Advanced Malignant Melanoma Clin. Cancer Res., March 15, 2009; 15(6): 2166 - 2173. [Abstract] [Full Text] [PDF] M. Schnurr, M. Orban, N. C. Robson, A. Shin, H. Braley, D. Airey, J. Cebon, E. Maraskovsky, and S. Endres ISCOMATRIX Adjuvant Induces Efficient Cross-Presentation of Tumor Antigen by Dendritic Cells via Rapid Cytosolic Antigen Delivery and Processing via Tripeptidyl Peptidase II J. Immunol., February 1, 2009; 182(3): 1253 - 1259. [Abstract] [Full Text] [PDF] L. M. Ebert, Y. C. Liu, C. S. Clements, N. C. Robson, H. M. Jackson, J. L. Markby, N. Dimopoulos, B. S. Tan, I. F. Luescher, I. D. Davis, et al. A Long, Naturally Presented Immunodominant Epitope from NY-ESO-1 Tumor Antigen: Implications for Cancer Vaccine Design Cancer Res., February 1, 2009; 69(3): 1046 - 1054. [Abstract] [Full Text] [PDF] N. C. Robson, D. J. Phillips, T. McAlpine, A. Shin, S. Svobodova, T. Toy, V. Pillay, N. Kirkpatrick, D. Zanker, K. Wilson, et al. Activin-A: a novel dendritic cell-derived cytokine that potently attenuates CD40 ligand-specific cytokine and chemokine production Blood, March 1, 2008; 111(5): 2733 - 2743. [Abstract] [Full Text] [PDF] P. Schnorrer, G. M. N. Behrens, N. S. Wilson, J. L. Pooley, C. M. Smith, D. El-Sukkari, G. Davey, F. Kupresanin, M. Li, E. Maraskovsky, et al. The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture PNAS, July 11, 2006; 103(28): 10729 - 10734. [Abstract] [Full Text] [PDF] F. Neumann, C. Wagner, K.-D. Preuss, B. Kubuschok, C. Schormann, S. Stevanovic, and M. Pfreundschuh Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells Blood, November 1, 2005; 106(9): 3105 - 3113. [Abstract] [Full Text] [PDF]

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