机构：[1]Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun 130021, P.R. China.[2]Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P.R. China.[3]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.外科系统普通外科首都医科大学宣武医院[4]School of Applied Chemistry and Engineering, University of Sciences and Technology of China, Hefei 230026, China.
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.
基金：
National Natural Science
Foundation of China (Grants 52073279 for N.S., 52025035
and 51873206 for Z.T., and 51833010 and 51520105004 for
X.C.), the Youth Innovation Promotion Association of Chinese
Academy of Sciences (Grant 2022224 for N.S.), the National
key research and development program of China (Grant
2021YFC2400603 for G.W.), and the Young and middle-aged
leading talents and teams of scientific and technological
innovation of Jilin Provincial Department of science and
technology (Grant 20200301001RQ for G.W.).
第一作者机构：[1]Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun 130021, P.R. China.
通讯作者：
通讯机构：[1]Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun 130021, P.R. China.[2]Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P.R. China.[4]School of Applied Chemistry and Engineering, University of Sciences and Technology of China, Hefei 230026, China.[*1]Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P.R. China[*2]Key Laboratory of Zoonosis Research, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun 130021, P.R. China[*3]School of Applied Chemistry and Engineering, University of Sciences and Technology of China, Hefei 230026, China
推荐引用方式(GB/T 7714)：
Yao Haochen,Shen Na,Ji Guofeng,et al.Cisplatin Nanoparticles Promote Intratumoral CD8+ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk.[J].NANO LETTERS.2022,22(8):3328-3339.doi:10.1021/acs.nanolett.2c00478.
APA：
Yao Haochen,Shen Na,Ji Guofeng,Huang Juanjuan,Sun Jiali...&Chen Xuesi.(2022).Cisplatin Nanoparticles Promote Intratumoral CD8+ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk..NANO LETTERS,22,(8)
MLA：
Yao Haochen,et al."Cisplatin Nanoparticles Promote Intratumoral CD8+ T Cell Priming via Antigen Presentation and T Cell Receptor Crosstalk.".NANO LETTERS 22..8(2022):3328-3339
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