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Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity

文献类型：期刊论文

作者Yang, Mengdie6,7; Liu, Haipeng5; Lou, Jingjing4; Zhang, Jiajia6,7; Zuo, Changjing3; Zhu, Mengqin6,7; Zhang, Xiaoyi6,7; Yin, Yuzhen6,7; Zhang, Yu6,7; Qin, Shanshan6,7
刊名SMALL
出版日期2023-10-16
页码15
关键词alpha-emitter immunogenic cell death pyroptosis radium-223 stimulator of interferon genes (STING)
ISSN号1613-6810
DOI10.1002/smll.202307448
通讯作者Cheng, Chao(chengchao1999@smmu.edu.cn) ; Cheng, Zhen(zcheng@simm.ac.cn) ; Yu, Fei(0910110013yufei@tongji.edu.cn)
英文摘要Radium-223 (223Ra) is the first-in-class alpha-emitter to mediate tumor eradication, which is commonly thought to kill tumor cells by directly cleaving double-strand DNA. However, the immunogenic characteristics and cell death modalities triggered by 223Ra remain unclear. Here, it is reported that the 223Ra irradiation induces the pro-inflammatory damage-associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death. Mechanically, 223Ra-induced DNA damage leads to the activation of stimulator of interferon genes (STING)-mediated DNA sensing pathway, which is critical for NLRP3 inflammasome-dependent pyroptosis and subsequent DCs maturation as well as T cell activation. These findings establish an essential role of STING in mediating alpha-emitter 223Ra-induced antitumor immunity, which provides the basis for the development of novel cancer therapeutic strategies and combinatory therapy. Alpha-emitter 223Ra can activate the stimulator of interferon genes (STING) signaling pathway by inducing DNA damage. Subsequently, the STING activates the NLRP3-dependent pyroptosis, a typical form of immunogenic cell death, to enhance antitumor immune response. this study highlights the pivotal role of the STING pathway in the effects of alpha-emitter 223Ra-induced pyroptosis, which leads even more opportunities for broadening the therapeutic window of alpha-emitter.image
WOS关键词IMMUNOGENIC CELL-DEATH ; IONIZING-RADIATION ; CANCER-PATIENTS ; OPEN-LABEL ; RADIOTHERAPY ; DICHLORIDE ; DOSIMETRY ; RADIONUCLIDES ; SURVIVAL ; THERAPY
资助项目This work was conducted with the supports by National Natural Science Foundation of China (Grant No. 82272030, 82071956, U2267221, 82272040). The Explorer Program of the Science and Technology Commission of Shanghai Municipality (22TS1400500), Special Foun[82272030] ; This work was conducted with the supports by National Natural Science Foundation of China (Grant No. 82272030, 82071956, U2267221, 82272040). The Explorer Program of the Science and Technology Commission of Shanghai Municipality (22TS1400500), Special Foun[82071956] ; This work was conducted with the supports by National Natural Science Foundation of China (Grant No. 82272030, 82071956, U2267221, 82272040). The Explorer Program of the Science and Technology Commission of Shanghai Municipality (22TS1400500), Special Foun[U2267221] ; This work was conducted with the supports by National Natural Science Foundation of China (Grant No. 82272030, 82071956, U2267221, 82272040). The Explorer Program of the Science and Technology Commission of Shanghai Municipality (22TS1400500), Special Foun[82272040] ; National Natural Science Foundation of China[22TS1400500] ; Explorer Program of the Science and Technology Commission of Shanghai Municipality[2022JC004] ; Special Foundation for Emerging Interdisciplinary Field Research of Shanghai Municipal Health Commission[PWYts2021-01] ; Pudong New Area Clinical Characteristic Discipline Project
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
WOS记录号WOS:001083065100001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/307397]  
专题新药研究国家重点实验室
通讯作者Cheng, Chao; Cheng, Zhen; Yu, Fei
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Naval Med Univ, Affiliated Hosp 1, Changhai Hosp, Dept Nucl Med, Shanghai 200433, Peoples R China
4.Fudan Univ, Pudong Med Ctr, Dept Nucl Med, Shanghai 201399, Peoples R China
5.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Clin Translat Res Ctr, Shanghai 200433, Peoples R China
6.Tongji Univ, Sch Med, Inst Nucl Med, Shanghai 200072, Peoples R China
7.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Nucl Med, Shanghai 200072, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Mengdie,Liu, Haipeng,Lou, Jingjing,et al. Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity[J]. SMALL,2023:15.
APA Yang, Mengdie.,Liu, Haipeng.,Lou, Jingjing.,Zhang, Jiajia.,Zuo, Changjing.,...&Yu, Fei.(2023).Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity.SMALL,15.
MLA Yang, Mengdie,et al."Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity".SMALL (2023):15.

入库方式： OAI收割

来源：上海药物研究所

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