In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb
| ISSN: | 0014-2980 |
|---|---|
| DOI: | 10.1002/eji.200838958 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::210b2bd9f4a7affc1d88316cd292c3ca https://doi.org/10.1002/eji.200838958 |
| Rights: | CLOSED |
| Přírůstkové číslo: | edsair.doi.dedup.....210b2bd9f4a7affc1d88316cd292c3ca |
| Autor: | Sarai Solano, Arantza Azpilikueta, Carmen Berasain, Asis Palazon, Carlos Alfaro, Oihana Murillo, Pedro Berraondo, Ignacio Melero, Ainhoa Arina, Maria C. Ochoa, Jose Luis Perez-Gracia, Juan Dubrot, Sandra Hervas-Stubbs, Izaskun Gabari |
| Rok vydání: | 2009 |
| Předmět: |
Ovalbumin
CD137 (4-1BB) Immunology Antigen presentation Mice Transgenic Biology DC Epitope Mice Tumor Necrosis Factor Receptor Superfamily Member 9 Cross-Priming Antigen Antigens Neoplasm Cell Line Tumor Neoplasms Tumor immunity Animals Immunology and Allergy Diphtheria toxin Antigen Presentation CD137 Antibodies Monoclonal Dendritic Cells Molecular biology Peptide Fragments Tumor antigen Mice Inbred C57BL CTL Cross-priming Ex vivo T-Lymphocytes Cytotoxic |
| Zdroj: | European Journal of Immunology. 39:2424-2436 |
| ISSN: | 0014-2980 |
| DOI: | 10.1002/eji.200838958 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text