Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1
文献类型：期刊论文
| 作者 | Ding, Ling1,2; Guo, Hongjie2,6; Zhang, Jie2; Zheng, Mingming2; Zhang, Wenjie2; Wang, Longsheng2; Du, Qianqian2; Zhou, Chen2; Xu, Yanjun3; Wu, Honghai2 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2024-09-04 |
| 关键词 | ABCB1 autophagy ER retention PD-L1 zosuquidar |
| DOI | 10.1002/advs.202400340 |
| 通讯作者 | He, Qiaojun(qiaojunhe@zju.edu.cn) ; Yang, Bo(yang924@zju.edu.cn) |
| 英文摘要 | The intracellular distribution and transportation process are essential for maintaining PD-L1 (programmed death-ligand 1) expression, and intervening in this cellular process may provide promising therapeutic strategies. Here, through a cell-based high content screening, it is found that the ABCB1 (ATP binding cassette subfamily B member 1) modulator zosuquidar dramatically suppresses PD-L1 expression by triggering its autophagic degradation. Mechanistically, ABCB1 interacts with PD-L1 and impairs COP II-mediated PD-L1 transport from ER (endoplasmic reticulum) to Golgi apparatus. The treatment of zosuquidar enhances ABCB1-PD-L1 interaction and leads the ER retention of PD-L1, which is subsequently degraded in the SQSTM1-dependent selective autophagy pathway. In CT26 mouse model and a humanized xenograft mouse model, zosuquidar significantly suppresses tumor growth and accompanies by increased infiltration of cytotoxic T cells. In summary, this study indicates that ABCB1 serves as a negative regulator of PD-L1, and zosuquidar may act as a potential immunotherapy agent by triggering PD-L1 degradation in the early secretory pathway. Newly synthesized programmed death-ligand 1 (PD-L1) needs to be sequentially transported to endoplasmic reticulum (ER) and Golgi apparatus for post-translational modification. The adenosine 5'-triphosphate (ATP) binding cassette subfamily B member 1 (ABCB1) modulator zosuquidar disrupts PD-L1 translocating from ER to Golgi apparatus, dramatically triggers autophagic degradation of PD-L1, and exhibits significant anti-tumor effect in vivo. image |
| WOS关键词 | P-GLYCOPROTEIN ; CANCER ; RESISTANCE ; TRIHYDROCHLORIDE ; IMMUNOTHERAPY ; COMBINATION ; INHIBITION ; MODULATION ; THERAPY |
| 资助项目 | National Natural Science Foundation of China[82330114] ; National Natural Science Foundation of China[82273949] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001304045500001 |
| 出版者 | WILEY |
| 资助机构 | National Natural Science Foundation of China |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/134960]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | He, Qiaojun; Yang, Bo |
| 作者单位 | 1.Nanhu Brain Comp Interface Inst, Hangzhou 311100, Peoples R China 2.Zhejiang Univ, Inst Pharmacol & Toxicol, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou 310058, Peoples R China 3.Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Peoples R China 4.Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Hangzhou 310018, Peoples R China 5.Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China 6.Hangzhou City Univ, Sch Med, Hangzhou 310015, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ding, Ling,Guo, Hongjie,Zhang, Jie,et al. Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1[J]. ADVANCED SCIENCE,2024. |
| APA | Ding, Ling.,Guo, Hongjie.,Zhang, Jie.,Zheng, Mingming.,Zhang, Wenjie.,...&Yang, Bo.(2024).Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1.ADVANCED SCIENCE. |
| MLA | Ding, Ling,et al."Zosuquidar Promotes Antitumor Immunity by Inducing Autophagic Degradation of PD-L1".ADVANCED SCIENCE (2024). |
入库方式： OAI收割
来源：合肥物质科学研究院
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