靜脈接種納米粒子疫苗可產生幹細胞樣TCF1+新抗原特異性CD8+ T細胞
作者：
小柯機器人發布時間：2020/11/4 16:58:48
美國國立衛生研究院Robert A. Seder研究組的研究顯示，通過靜脈接種納米粒子疫苗可產生幹細胞樣TCF1+新抗原特異性CD8+ T細胞。該項研究成果發表在2020年11月2日出版的《自然-免疫學》上。
使用將新抗原肽連接到Toll樣受體7/8激動劑（SNP-7/8a）的自組裝納米顆粒疫苗，研究人員探究了給藥途徑和劑量如何改變新抗原特異性CD8+ T細胞的數量和質量。與皮下免疫（SNP-SC）相比，靜脈注射（SNP-IV）誘導更高比例的TCF1+ PD-1+ CD8+ T細胞。單細胞RNA測序表明SNP-IV誘導幹細胞樣基因（Tcf7、Slamf6、Xcl1）表達，而SNP-SC則誘導了效應基因（Gzmb、Klrg1、Cx3cr1）的產生。
在檢查點封鎖後，由SNP-IV產生的幹細胞樣細胞增殖並分化為效應細胞，與治療模型中的SNP-SC相比，可產生更有效的抗腫瘤反應。樹突狀細胞呈遞抗原的持續時間控制著CD8+ T細胞的數量和質量。這些數據證明了可以通過針對特定效應子或幹細胞樣CD8+T細胞的生成來調節疫苗參數從而優化抗腫瘤免疫。
研究人員表示，個性化癌症疫苗是誘導T細胞對腫瘤新抗原產生免疫的潛在方法。
附：英文原文
Title: Intravenous nanoparticle vaccination generates stem-like TCF1 + neoantigen-specific CD8 + T cells
Author: Faezzah Baharom, Ramiro A. Ramirez-Valdez, Kennedy K. S. Tobin, Hidehiro Yamane, Charles-Antoine Dutertre, Ahad Khalilnezhad, Glennys V. Reynoso, Vincent L. Coble, Geoffrey M. Lynn, Matthew P. Mul, Andrew J. Martins, John P. Finnigan, Xiao Meng Zhang, Jessica A. Hamerman, Nina Bhardwaj, John S. Tsang, Heather D. Hickman, Florent Ginhoux, Andrew S. Ishizuka, Robert A. Seder
Issue&Volume: 2020-11-02
Abstract: 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.
DOI: 10.1038/s41590-020-00810-3
Source: https://www.nature.com/articles/s41590-020-00810-3