Tumor growth enhances cross-presentation leading to limited T cell activation without tolerance |
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| Authors: | Nguyen Linh T Elford Alisha R Murakami Kiichi Garza Kristine M Schoenberger Stephen P Odermatt Bernhard Speiser Daniel E Ohashi Pamela S |
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| Affiliation: | Departments of Immunology and Medical Biophysics, Ontario Cancer Institute, 610 University Ave., Toronto, Ontario M5G 2M9, Canada. |
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| 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. |
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