Intravenous Nanoparticle Vaccination Generates Stem-Like TCF1+ Neoantigen-Specific CD8+ T Cells
| العنوان: | Intravenous Nanoparticle Vaccination Generates Stem-Like TCF1+ Neoantigen-Specific CD8+ T Cells |
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| المؤلفون: | Hidehiro Yamane, Geoffrey M. Lynn, Charles-Antoine Dutertre, John P. Finnigan, Nina Bhardwaj, Matthew P. Mulé, John S. Tsang, Glennys V. Reynoso, Vincent L. Coble, Jessica A. Hamerman, Xiao Meng Zhang, Kennedy Tobin, Andrew S. Ishizuka, Faezzah Baharom, Ramiro A. Ramirez-Valdez, Florent Ginhoux, Robert A. Seder, Heather D. Hickman, Ahad Khalilnezhad, Andrew J. Martins |
| المصدر: | Nature immunology |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_treatment, Immunology, Antigen presentation, CD8-Positive T-Lymphocytes, Cancer Vaccines, Article, GZMB, 03 medical and health sciences, Mice, 0302 clinical medicine, Antigens, Neoplasm, medicine, Immunology and Allergy, Cytotoxic T cell, Animals, Hepatocyte Nuclear Factor 1-alpha, Antigen Presentation, Effector, Chemistry, Vaccination, Dendritic Cells, Immunity, Innate, Mice, Inbred C57BL, 030104 developmental biology, Immunization, Cancer research, Nanoparticles, Female, Adjuvant, CD8, 030215 immunology, XCL1 |
| الوصف: | Personalized cancer vaccines are a promising approach for inducing T cell immunity to tumor neoantigens. Using a self-assembling nanoparticle vaccine that links neoantigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we show how the route and dose alter the magnitude and quality of neoantigen-specific CD8+ T cells. Intravenous vaccination (SNP-IV) induced a higher proportion of TCF1+PD-1+CD8+ T cells as compared to subcutaneous immunization (SNP-SC). Single-cell RNA sequencing showed that SNP-IV induced stem-like genes (Tcf7, Slamf6, Xcl1) whereas SNP-SC enriched for effector genes (Gzmb, Klrg1, Cx3cr1). Stem-like cells generated by SNP-IV proliferated and differentiated into effector cells upon checkpoint blockade, leading to superior antitumor response as compared to SNP-SC in a therapeutic model. The duration of antigen presentation by dendritic cells controlled the magnitude and quality of CD8+ T cells. These data demonstrate how to optimize antitumor immunity by modulating vaccine parameters for specific generation of effector or stem-like CD8+ T cells. Seder and colleagues use a self-assembling nanoparticle vaccine and adjuvant to expand stem-like CD8+ T cells and trigger potent antitumor responses. |
| اللغة: | English |
| تدمد: | 1529-2916 1529-2908 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7fcfbea9dd3f09b85a4cef16cce85b0e http://europepmc.org/articles/PMC7746638 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7fcfbea9dd3f09b85a4cef16cce85b0e |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15292916 15292908 |
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