CD8型
T细胞受体
细胞毒性T细胞
癌症研究
癌症免疫疗法
免疫疗法
启动(农业)
免疫系统
T细胞
顺铂
化学
抗原
细胞生物学
免疫学
生物
医学
生物化学
化疗
内科学
体外
发芽
植物
作者
Haochen Yao,Na Shen,Guofeng Ji,Juanjuan Huang,Jiali Sun,Guoqing Wang,Zhaohui Tang,Xuesi Chen
出处
期刊:Nano Letters
[American Chemical Society]
日期:2022-04-11
卷期号:22 (8): 3328-3339
被引量:18
标识
DOI:10.1021/acs.nanolett.2c00478
摘要
Nanomedicines are highly promising for cancer therapy due to their minimal side effects. However, little is known regarding their host immune response, which may limit their clinical efficacy and applications. Here, we find that cisplatin (CDDP)-loaded poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol) complex nanoparticles (CDDP-NPs) elicit a strong antitumor CD8+ T cell-mediated immune response in a tumor-bearing mouse model compared to free CDDP. Mechanistically, the sustained retention of CDDP-NPs results in persistent tumor MHC-I overexpression, which promotes the formation of MHC-I-antigen peptide complex (pMHC-I), enhances the interaction between pMHC-I and T cell receptor (TCR), and leads to the activation of TCR signaling pathway and CD8+ T cell-mediated immune response. Furthermore, CDDP-NPs upregulate the costimulatory OX40 on intratumoral CD8+ T cells, and synergize with the agonistic OX40 antibody (aOX40) to suppress tumor growth by 89.2%. Our study provides a basis for the efficacy advantage of CDDP-based nanomedicines and immunotherapy.
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