Cisplatin Nanoparticles Promote Intratumoral CD8+ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk

• DOI: 10.1021/acs.nanolett.2c00478
• Publication Date: 2022-04-11T20:43:54Z
• Authors: Haochen Yao; Na Shen; Guofeng Ji; Juanjuan Huang; Jiali Sun; Guoqing Wang; Zhaohui Tang; Xuesi Chen
• Keywords: Cancer Immunotherapy; Priming (agriculture)

Nanomedicines are highly promising for cancer therapy due to their minimal side effects. However, little is known regarding host immune response, which may limit 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 response in tumor-bearing mouse model compared free CDDP. Mechanistically, the sustained retention of CDDP-NPs results persistent tumor MHC-I overexpression, promotes formation MHC-I-antigen peptide (pMHC-I), enhances interaction between pMHC-I cell receptor (TCR), leads activation TCR signaling pathway response. Furthermore, upregulate costimulatory OX40 on intratumoral cells, synergize with agonistic antibody (aOX40) suppress growth by 89.2%. Our study provides basis advantage CDDP-based nanomedicines immunotherapy.