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Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment

文献类型：期刊论文

作者Wang, Shuang2; Li, Feng2,3; Ye, Tong2,3; Wang, Jianghua2,3; Lyu, Chengliang2; Qing, Shuang2,3; Ding, Zhaowen2,3; Gao, Xiaoyong2; Jia, Rongrong4; Yu, Di1
刊名SCIENCE TRANSLATIONAL MEDICINE
出版日期2021-10-13
卷号13期号:615页码:18
ISSN号1946-6234
DOI10.1126/scitranslmed.abb6981
英文摘要Despite multiple immunotherapeutic technologies that achieve potent T cell activation, effector T cells still lack efficiency because of the highly immunosuppressive conditions in the tumor microenvironment. Inspired by recent advances in nano-sized secreted vesicles known as exosomes as therapeutic agents and research revealing that circulating cancer cells have a "homing" capacity to return to the main tumor sites, we generated macrophage-tumor hybrid cells. We introduced nuclei isolated from tumor cells into activated M1-like macrophages to produce chimeric exosomes (aMT-exos). The aMT-exos were able to accumulate in both lymph nodes and diverse tumors of xenograft mice. They entered lymph nodes and primed T cell activation in both the classical antigen-presenting cell-induced immunostimulatory manner and a unique "direct exosome interaction"manner. aMT-exos also had strong "homing behavior" to tumor sites, where they ameliorated immunosuppression. They were effective in inducing tumor regression and extending survival in primary mouse models of lymphoma and breast and melanoma cancers. In addition, when combined with anti-programmed death 1 (a-PD1) treatment, aMT-exos were able to extend survival of metastatic and postsurgical tumor recurrence mouse models. Such a coactivation of the immune response and the tumor microenvironment enabled aMT-exos to confer efficient inhibition of primary tumors, tumor metastases, and postoperative tumor recurrence for personalized immunotherapy, which warrants further exploration in the clinical setting.
WOS关键词METASTATIC NICHE FORMATION ; IN-VIVO DEPLETION ; DENDRITIC CELLS ; T-CELLS ; CANCER ; VACCINE ; SUPPRESSION ; THERAPY ; CD19
资助项目National Natural Science Foundation of China[32030062] ; National Natural Science Foundation of China[21821005] ; National Natural Science Foundation of China[U2001224] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB29040303] ; National Key R&D Program of China[2017YFA0207900] ; State Key Laboratory of Biochemical Engineering[2019KF-01] ; China Postdoctoral Science Foundation[2019 M650850]
WOS研究方向Cell Biology ; Research & Experimental Medicine
语种英语
WOS记录号WOS:000707525800002
出版者AMER ASSOC ADVANCEMENT SCIENCE
资助机构National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; State Key Laboratory of Biochemical Engineering ; China Postdoctoral Science Foundation
源URL[http://ir.ipe.ac.cn/handle/122111/50563]  
专题中国科学院过程工程研究所
通讯作者Wei, Wei; Ma, Guanghui
作者单位1.Univ Queensland, Diamantina Inst, Fac Med, Translat Res Inst, Brisbane, Qld 4102, Australia
2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
3.Univ Chinese Acad Sci, Sch Chem Engn, Beijing 100049, Peoples R China
4.Shanghai Jiao Tong Univ, Shanghai Tongren Hosp, Dept Gastroenterol, Sch Med, Shanghai 200336, Peoples R China
5.Capital Med Univ, Canc Ctr, Beijing Shijitan Hosp, Dept Med Oncol,Beijing Key Lab Therapeut Canc Vac, Beijing 100038, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Shuang,Li, Feng,Ye, Tong,et al. Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment[J]. SCIENCE TRANSLATIONAL MEDICINE,2021,13(615):18.
APA Wang, Shuang.,Li, Feng.,Ye, Tong.,Wang, Jianghua.,Lyu, Chengliang.,...&Ma, Guanghui.(2021).Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment.SCIENCE TRANSLATIONAL MEDICINE,13(615),18.
MLA Wang, Shuang,et al."Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment".SCIENCE TRANSLATIONAL MEDICINE 13.615(2021):18.

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来源：过程工程研究所

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