Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance
Details
State: Serval
Version: author
Serval ID
serval:BIB_061A829BB9D3
Type
Article: article from journal or magazin.
Collection
Publications
Fund
Title
Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance
Journal
Journal of Experimental Medicine
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
02/2002
Volume
195
Number
4
Pages
423-35
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb 18
Research Support, Non-U.S. Gov't --- Old month value: Feb 18
Abstract
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.
Keywords
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
Create date
28/01/2008 12:33
Last modification date
03/03/2018 13:25