Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer.

Autor: van der Gracht ET; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands., Schoonderwoerd MJ; Department of Gasteroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., van Duikeren S; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands., Yilmaz AN; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands., Behr FM; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands., Colston JM; Nuffield Department of Medicine, University of Oxford, Oxford, UK., Lee LN; Nuffield Department of Medicine, University of Oxford, Oxford, UK., Yagita H; Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan., van Gisbergen KP; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands., Hawinkels LJ; Department of Gasteroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands., Koning F; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands., Klenerman P; Nuffield Department of Medicine, University of Oxford, Oxford, UK., Arens R; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands r.arens@lumc.nl.
Jazyk: angličtina
Zdroj: Journal for immunotherapy of cancer [J Immunother Cancer] 2020 Dec; Vol. 8 (2).
DOI: 10.1136/jitc-2020-001133
Abstrakt: Background: Adenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8 + T cells elicited upon immunization with adenoviral vectors.
Methods: Adenoviral vaccine vectors encoding the full-length E7 protein from human papilloma virus (HPV) or the immunodominant epitope from E7 were generated, and mice were immunized intravenously with different quantities (10 7 , 10 8 or 10 9 infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated.
Results: The adenoviral vaccines elicited inflationary E7-specific memory CD8 + T cell responses in a dose-dependent manner. The magnitude of these vaccine-specific CD8 + T cells in the circulation related to the development of E7-specific CD8 + tissue-resident memory T (T RM ) cells, which were maintained for months in multiple tissues after vaccination. The vaccine-specific CD8 + T cell responses conferred long-term protection against HPV-induced carcinomas in the skin and liver, and this protection required the induction and accumulation of CD8 + T RM cells. Moreover, the formation of CD8 + T RM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization.
Conclusions: Together, these data show that adenoviral vector-induced CD8 + T cell inflation promotes protective T RM cell populations, and this can be enhanced by targeting CTLA-4.
Competing Interests: Competing interests: No, there are no competing interests.
(© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze: MEDLINE
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