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Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer
Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer
- Source :
- Journal for ImmunoTherapy of Cancer, Vol 8, Iss 2 (2020), Journal for Immunotherapy of Cancer, Journal for ImmunoTherapy of Cancer, 8(2). BMJ PUBLISHING GROUP
- Publication Year :
- 2020
- Publisher :
- BMJ Publishing Group, 2020.
-
Abstract
- BackgroundAdenoviral 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.MethodsAdenoviral 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 (107, 108 or 109 infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated.ResultsThe 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 (TRM) 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+ TRM cells. Moreover, the formation of CD8+ TRM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization.ConclusionsTogether, these data show that adenoviral vector-induced CD8+ T cell inflation promotes protective TRM cell populations, and this can be enhanced by targeting CTLA-4.
- Subjects :
- 0301 basic medicine
CTLA-4 antigen
Cancer Research
T cell
Immunology
Biology
Cancer Vaccines
Epitope
03 medical and health sciences
Mice
0302 clinical medicine
Neoplasms
medicine
Immunology and Allergy
Animals
Humans
RC254-282
Pharmacology
CD86
immunologic memory
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Basic Tumor Immunology
adaptive immunity
Acquired immune system
vaccination
030104 developmental biology
medicine.anatomical_structure
Oncology
Immunization
Cancer research
Molecular Medicine
CD8-positive T-lymphocytes
Immunotherapy
Memory T cell
CD80
CD8
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 20511426
- Volume :
- 8
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal for ImmunoTherapy of Cancer
- Accession number :
- edsair.doi.dedup.....4847032c5166ee69620b25fd39734989