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PMID: 11854356 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 195 ·No. 4 ·2002-02-18 ·Pages 423-35

Nguyen LT, Elford AR, Murakami K, Garza KM, Schoenberger SP, Odermatt B, Speiser DE, Ohashi PS

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.

MeSH Terms
Adoptive Transfer Animals Antibodies, Monoclonal/immunology Antigen Presentation Antigens, Neoplasm/immunology Antigens, Tumor-Associated, Carbohydrate/administration & dosage,immunology CD40 Antigens/immunology Cell Division Flow Cytometry Hyaluronan Receptors/immunology,metabolism 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
Chemicals
Antibodies, Monoclonal Antigens, Neoplasm Antigens, Tumor-Associated, Carbohydrate CD40 Antigens Hyaluronan Receptors
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Nguyen Linh T
Departments of Immunology and Medical Biophysics, Ontario Cancer Institute, 610 University Ave., Toronto, Ontario M5G 2M9, Canada.
Elford Alisha R
Murakami Kiichi
Garza Kristine M
Schoenberger Stephen P
Odermatt Bernhard
Speiser Daniel E
Ohashi Pamela S
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20010032
Published
2002-02-18
Pages
423-35
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193619
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20010032 PMC Full Text View journal details
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