Tumor-repopulating cell-derived microparticles elicit cascade amplification of chemotherapy-induced antitumor immunity to boost anti-PD-1 therapy

作     者：Nana Bie Tuying Yong Zhaohan Wei Qingle Liang Xiaoqiong Zhang Shiyu Li Xin Li Jianye Li Lu Gan Xiangliang Yang Nana Bie;Tuying Yong;Zhaohan Wei;Qingle Liang;Xiaoqiong Zhang;Shiyu Li;Xin Li;Jianye Li;Lu Gan;Xiangliang Yang

作者机构：National Engineering Research Center for NanomedicineCollege of Life Science and TechnologyHuazhong University of Science and Technology430074WuhanChina Key Laboratory of Molecular Biophysics of the Ministry of EducationCollege of Life Science and TechnologyHuazhong University of Science and Technology430074WuhanChina Hubei Key Laboratory of Bioinorganic Chemistry and Materia MedicaHuazhong University of Science and Technology430074WuhanChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2023年第8卷第11期

页      面：5539-5555页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：National Key R&D Program of China(2020YFA0710700,2022YFA1206000 and 2021YFA1201200) National Natural Science Foundation of China(82272844,81974459,82073796,81627901 and 82202860) Program for HUST Academic Frontier Youth Team(2018QYTD01) Open Funds of State Key Laboratory of Oncology in South China(HN2022-07) 

主　　题：immunity chemotherapy boost 

摘      要：Immune checkpoint blockade(ICB)therapy,particularly antibodies targeting the programmed death receptor 1(PD-1)and its ligand(PD-L1),has revolutionized cancer ***,its efficacy as a standalone therapy remains *** ICB therapy in combination with chemotherapy shows promising therapeutic responses,the challenge lies in amplifying chemotherapy-induced antitumor immunity *** relies on efficient drug delivery to tumor cells and robust antigen presentation by dendritic cells(DCs).Here,we developed tumor-repopulating cell(TRC)-derived microparticles with exceptional tumor targeting to deliver doxorubicin(DOX@3D-MPs)for improve anti-PD-1 ***@3D-MPs effectively elicit immunogenic tumor cell death to release sufficient tumor *** shock protein 70(HSP70)overexpressed in DOX@3D-MPs contributes to capturing tumor antigens,promoting their phagocytosis by DCs,and facilitating DCs maturation,leading to the activation of CD8+T ***@3D-MPs significantly enhance the curative response of anti-PD-1 treatment in large subcutaneous H22 hepatoma,orthotopic 4T1 breast tumor and Panc02 pancreatic tumor *** results demonstrate that DOX@3D-MPs hold promise as agents to improve the response rate to ICB therapy and generate long-lasting immune memory to prevent tumor relapse.