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

Nanomedicines are highly promising for cancer therapy due to theirminimal side effects. However, little is known regarding their host immune response,which may limit their clinical efficacy and applications. Here, wefind that cisplatin(CDDP)-loaded poly(L-glutamic acid)-graft-methoxy poly(ethylene glycol) complexnanoparticles (CDDP-NPs) elicit a strong antitumor CD8+T cell-mediated immuneresponse in a tumor-bearing mouse model compared to free CDDP. Mechanistically, thesustained retention of CDDP-NPs results in persistent tumor MHC-I overexpression,which promotes the formation of MHC-I-antigen peptide complex (pMHC-I), enhancesthe interaction between pMHC-I and T cell receptor (TCR), and leads to the activation ofTCR signaling pathway and CD8+T cell-mediated immune response. Furthermore,CDDP-NPs upregulate the costimulatory OX40 on intratumoral CD8+T cells, andsynergize 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 immuno therapy