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Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Zhang Xiaoqiong[1] * ; Wei Zhaohan[1] * ; Yong Tuying[1,2,3,4] * ; Li Shiyu[1] ; Bie Nana[1] ; Li Jianye[1] ; Li Xin[1] ; Liu Haojie[1] ; Xu Hang[2] ; Yan Yuchen[1] ; Zhang Bixiang[5] ; Chen Xiaoping[5] ; Yang Xiangliang[1,2,3,4] ; Gan Lu[1,2,3,4] ;
单位： [1]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China [2]Key Laboratory ofMolecular Biophysics of the Ministry of Education, College of Life Science and Technology,Huazhong University of Science and Technology, Wuhan, China [3]Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan, China [4]Hubei Bioinformatics and Molecular Imaging Key Laboratory, Huazhong University of Science and Technology, Wuhan, China [5]Hepatic SurgeryCenter, Tongji Hospital, TongjiMedical College, Huazhong University of Science and Technology,Wuhan, China.
出处：
DOI： 10.1038/s41467-023-41438-9
ISSN：

摘要：
The durable response rate to immune checkpoint blockade such as anti-programmed cell death-1 (PD-1) antibody remains relatively low in hepatocellular carcinoma (HCC), mainly depending on an immunosuppressive microenvironment with limited number of CD8+ T cells, especially stem-like CD8+ T cells, in tumor tissues. Here we develop engineered microparticles (MPs) derived from alpha-fetoprotein (AFP)-overexpressing macrophages to load resiquimod (R848@M2pep-MPsAFP) for enhanced anti-PD-1 therapy in HCC. R848@M2pep-MPsAFP target and reprogram immunosuppressive M2-like tumor-associated macrophages (TAMs) into M1-like phenotype. Meanwhile, R848@M2pep-MPsAFP-reprogrammed TAMs act as antigen-presenting cells, not only presenting AFP antigen to activate CD8+ T cell-mediated antitumor immunity, but also providing an intra-tumoral niche to maintain and differentiate stem-like CD8+ T cells. Combination immunotherapy with anti-PD-1 antibody generates strong antitumor immune memory and induces abundant stem-like CD8+ T cell proliferation and differentiation to terminally exhausted CD8+ T cells for long-term immune surveillance in orthotopic and autochthonous HCC preclinical models in male mice. We also show that the R848-loaded engineered MPs derived from macrophages overexpressing a model antigen ovalbumin (OVA) can improve anti-PD-1 therapy in melanoma B16-OVA tumor-bearing mice. Our work presents a facile and generic strategy for personalized cancer immunotherapy to boost anti-PD-1 therapy.© 2023. Springer Nature Limited.

基金：
This work was supported by the National Key R&D Program of China (2020YFA0710700 to L.G., and 2022YFA1206000 and 2021YFA1201200 to T.Y.), National Natural Science Foundation of China (82272844 and 81974459 to L.G., 82073796 and 81627901 to X.Y., and 82203061 to Z.W.), China Postdoctoral Science Foundation (2022M721260 to Z.W. and 2023M731213 to X.Z.), Program for HUST Academic Frontier Youth Team (2018QYTD01 to L.G.) and Open Funds of State Key Laboratory of Oncology in South China (HN2022-07 to T.Y.).
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外文
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出版当年[2022]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2025]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
JCR分区：
出版当年[2021]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
共同第一作者：
通讯作者：
通讯机构： [1]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China [2]Key Laboratory ofMolecular Biophysics of the Ministry of Education, College of Life Science and Technology,Huazhong University of Science and Technology, Wuhan, China [3]Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan, China [4]Hubei Bioinformatics and Molecular Imaging Key Laboratory, Huazhong University of Science and Technology, Wuhan, China
推荐引用方式(GB/T 7714)：
Zhang Xiaoqiong,Wei Zhaohan,Yong Tuying,et al.Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy[J].NATURE COMMUNICATIONS.2023,14(1):doi:10.1038/s41467-023-41438-9.
APA：
Zhang Xiaoqiong,Wei Zhaohan,Yong Tuying,Li Shiyu,Bie Nana...&Gan Lu.(2023).Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy.NATURE COMMUNICATIONS,14,(1)
MLA：
Zhang Xiaoqiong,et al."Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy".NATURE COMMUNICATIONS 14..1(2023)

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