title: In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb.
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.
authors: Gene Therapy Unit, Centro de Investigación Médica Aplicada, Universidad de Navarra, Pamplona, Spain.
authors: Oihana
authors: O
authors: Murillo
authors: Juan
authors: J
authors: Dubrot
authors: Asís
authors: A
authors: Palazón
authors: Ainhoa
authors: A
authors: Arina
authors: Arantza
authors: A
authors: Azpilikueta
authors: Carlos
authors: C
authors: Alfaro
authors: Sarai
authors: S
authors: Solano
authors: María C
authors: MC
authors: Ochoa
authors: Carmen
authors: C
authors: Berasain
authors: Izaskun
authors: I
authors: Gabari
authors: José L
authors: JL
authors: Pérez-Gracia
authors: Pedro
authors: P
authors: Berraondo
authors: Sandra
authors: S
authors: Hervás-Stubbs
authors: Ignacio
authors: I
authors: Melero
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C110366:OVA-8; D010446:Peptide Fragments; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D010047:Ovalbumin