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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología terapia génica > DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista >

In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb
Authors: Murillo, O. (Oihana)
Dubrot, J. (Juan)
Palazon, A. (Asís)
Arina, A. (Ainhoa)
Azpilicueta, A. (Arantza)
Alfaro, C. (Carlos)
Solano, S. (Sarai)
Ochoa, M.C. (María Carmen)
Berasain, C. (Carmen)
Gabari, I. (Izaskun)
Perez-Gracia, J.L. (José Luis)
Berraondo, P. (Pedro)
Hervas-Stubbs, S. (Sandra)
Melero, I. (Ignacio)
Keywords: CD137 (4-1BB)
Cross-priming
CTL
DC
Tumor immunity
Issue Date: 2009
Publisher: Wiley-VCH Verlag Berlin
Publisher version: http://onlinelibrary.wiley.com/doi/10.1002/eji.200838958/abstract
ISSN: 1521-4141
Citation: Murillo O, Dubrot J, Palazon A, Arina A, Azpilikueta A, Alfaro C, et al. In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb. Eur J Immunol 2009 Sep;39(9):2424-2436.
Abstract
Anti-CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti-tumor effect involves co-stimulation of tumor-specific CD8(+) T cells. Whether antigen cross-presenting DC are required for the efficacy of anti-CD137 mAb treatment has never been examined. Here we show that the administration of anti-CD137 mAb eradicates EG7-OVA tumors by a strictly CD8beta(+) T-cell-dependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen cross-presentation revealed that CD11c(+) cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumor-draining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti-OVA CTL induction. Using CD11c diphtheria toxin receptor-green fluorescent protein-->C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross-presentation in CTL induction against OVA(257-264) epitope and in the antitumor efficacy induced by anti-CD137 mAb
Permanent link: http://hdl.handle.net/10171/21772
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Terapia génica del cáncer - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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