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Robust Iterative Stimulation with Self-Antigens Overcomes CD8+ T Cell Tolerance to Self- and Tumor Antigens.
Nelson, Christine E; Thompson, Emily A; Quarnstrom, Clare F; Fraser, Kathryn A; Seelig, Davis M; Bhela, Siddheshvar; Burbach, Brandon J; Masopust, David; Vezys, Vaiva.
Afiliación
  • Nelson CE; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Thompson EA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Quarnstrom CF; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Fraser KA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Seelig DM; Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN 55118, USA.
  • Bhela S; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Burbach BJ; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Masopust D; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Vezys V; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: vvezys@umn.edu.
Cell Rep ; 28(12): 3092-3104.e5, 2019 09 17.
Article en En | MEDLINE | ID: mdl-31533033
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+ 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+ 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+ T cells that can be used for cancer treatment.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Tolerancia Inmunológica / Inmunidad Celular / Melanoma / Antígenos de Neoplasias Límite: Animals Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Tolerancia Inmunológica / Inmunidad Celular / Melanoma / Antígenos de Neoplasias Límite: Animals Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos