Back to Search
Start Over
Robust Iterative Stimulation with Self-Antigens Overcomes CD8 + T Cell Tolerance to Self- and Tumor Antigens.
- Source :
-
Cell reports [Cell Rep] 2019 Sep 17; Vol. 28 (12), pp. 3092-3104.e5. - Publication Year :
- 2019
-
Abstract
- The immune system adapts to constitutive antigens to preserve self-tolerance, which is a major barrier for anti-tumor immunity. Antigen-specific reversal of tolerance constitutes a major goal to spur therapeutic applications. Here, we show that robust, iterative, systemic stimulation targeting tissue-specific antigens in the context of acute infections reverses established CD8 <superscript>+</superscript> T cell tolerance to self, including in T cells that survive negative selection. This strategy results in large numbers of circulating and resident memory self-specific CD8 <superscript>+</superscript> T cells that are widely distributed and can be co-opted to control established malignancies bearing self-antigen without concomitant autoimmunity. Targeted expansion of both self- and tumor neoantigen-specific T cells acts synergistically to boost anti-tumor immunity and elicits protection against aggressive melanoma. Our findings demonstrate that T cell tolerance can be re-adapted to responsiveness through robust antigenic exposure, generating self-specific CD8 <superscript>+</superscript> T cells that can be used for cancer treatment.<br /> (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 28
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 31533033
- Full Text :
- https://doi.org/10.1016/j.celrep.2019.08.038