Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_061A829BB9D3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance
Périodique
Journal of Experimental Medicine
Auteur(s)
Nguyen  L. T., Elford  A. R., Murakami  K., Garza  K. M., Schoenberger  S. P., Odermatt  B., Speiser  D. E., Ohashi  P. S.
ISSN
0022-1007 (Print)
Statut éditorial
Publié
Date de publication
02/2002
Volume
195
Numéro
4
Pages
423-35
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb 18
Résumé
Using a tumor model of spontaneously arising insulinomas expressing a defined tumor-associated antigen, we investigated whether tumor growth promotes cross-presentation and tolerance of tumor-specific T cells. We found that an advanced tumor burden enhanced cross-presentation of tumor-associated antigens to high avidity tumor-specific T cells, inducing T cell proliferation and limited effector function in vivo. However, contrary to other models, tumor-specific T cells were not tolerized despite a high tumor burden. In fact, in tumor-bearing mice, persistence and responsiveness of adoptively transferred tumor-specific T cells were enhanced. Accordingly, a potent T cell-mediated antitumor response could be elicited by intravenous administration of tumor-derived peptide and agonistic anti-CD40 antibody or viral immunization and reimmunization. Thus, in this model, tumor growth promotes activation of high avidity tumor-specific T cells instead of tolerance. Therefore, the host remains responsive to T cell immunotherapy.
Mots-clé
Adoptive Transfer Animals Antibodies, Monoclonal/immunology *Antigen Presentation Antigens, CD40/immunology Antigens, CD44/immunology/metabolism Antigens, Neoplasm/*immunology Antigens, Tumor-Associated, Carbohydrate/administration & dosage/immunology Cell Division Flow Cytometry Hypoglycemia/complications *Immune Tolerance Immunologic Surveillance Immunotherapy, Active Insulinoma/complications/*immunology/*pathology/therapy Lymph Nodes/immunology *Lymphocyte Activation Mice Mice, Transgenic Radiation Chimera Survival Analysis T-Lymphocytes, Cytotoxic/cytology/*immunology Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 11:33
Dernière modification de la notice
20/08/2019 12:28
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