期刊
NATURE IMMUNOLOGY
卷 22, 期 1, 页码 41-52出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-00810-3
关键词
-
类别
资金
- Intramural Research Program of the U.S. NIH
- EMBO YIP
- Singapore Immunology Network core funding
The study demonstrates that using a self-assembling nanoparticle vaccine and adjuvant can expand stem-like CD8(+) T cells, optimize anti-tumor immunity, and enhance the strength and effectiveness of the anti-tumor response.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据