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 

机构地区：[1]National Engineering Research Center for Nanomedicine,College of Life Science and Technology,Huazhong University of Science and Technology,430074,Wuhan,China [2]Key Laboratory of Molecular Biophysics of the Ministry of Education,College of Life Science and Technology,Huazhong University of Science and Technology,430074,Wuhan,China [3]Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica,Huazhong University of Science and Technology,430074,Wuhan,China

出　　处：《Signal Transduction and Targeted Therapy》2023年第11期5539-5555,共17页信号转导与靶向治疗（英文）

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).

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 treatment.However,its efficacy as a standalone therapy remains limited.Although ICB therapy in combination with chemotherapy shows promising therapeutic responses,the challenge lies in amplifying chemotherapy-induced antitumor immunity effectively.This 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 therapy.DOX@3D-MPs effectively elicit immunogenic tumor cell death to release sufficient tumor antigens.Heat 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 cells.DOX@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 models.These 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.

关 键 词：immunity CHEMOTHERAPY BOOST 

分 类 号：R730.51[医药卫生—肿瘤]