دورية أكاديمية
Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1
| العنوان: | Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1 |
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| المؤلفون: | Cha, Jong-Ho, Yang, Wen-Hao, Xia, Weiya, Wei, Yongkun, Chan, Li-Chuan, Lim, Seung-Oe, Li, Chia-Wei, Kim, Taewan, Chang, Shih-Shin, Lee, Heng-Huan, Hsu, Jennifer L, Wang, Hung-Ling, Kuo, Chu-Wei, Chang, Wei-Chao, Hadad, Sirwan, Purdie, Colin A, McCoy, Aaron M, Cai, Shirong, Tu, Yizheng, Litton, Jennifer K, Mittendorf, Elizabeth A, Moulder, Stacy L, Symmans, William F, Thompson, Alastair M, Piwnica-Worms, Helen, Chen, Chung-Hsuan, Khoo, Kay-Hooi, Hung, Mien-Chie |
| المصدر: | Cha , J-H , Yang , W-H , Xia , W , Wei , Y , Chan , L-C , Lim , S-O , Li , C-W , Kim , T , Chang , S-S , Lee , H-H , Hsu , J L , Wang , H-L , Kuo , C-W , Chang , W-C , Hadad , S , Purdie , C A , McCoy , A M , Cai , S , Tu , Y , Litton , J K , Mittendorf , E A , Moulder , S L , Symmans , W F , .... |
| سنة النشر: | 2018 |
| المجموعة: | Discovery - University of Dundee Online Publications |
| مصطلحات موضوعية: | cancer immunotherapy, ER accumulation, ERAD, glycosylation, immune checkpoint blockade, metformin, PD-L1, /dk/atira/pure/subjectarea/asjc/1300/1312, name=Molecular Biology, /dk/atira/pure/subjectarea/asjc/1300/1307, name=Cell Biology |
| الوصف: | Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1). Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by metformin directly phosphorylates S195 of PD-L1. S195 phosphorylation induces abnormal PD-L1 glycosylation, resulting in its ER accumulation and ER-associated protein degradation (ERAD). Consistently, tumor tissues from metformin-treated breast cancer patients exhibit reduced PD-L1 levels with AMPK activation. Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity against cancer cells. Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://discovery.dundee.ac.uk/en/publications/81b9c4e4-1d77-4814-a958-c40b9483aea7Test |
| DOI: | 10.1016/j.molcel.2018.07.030 |
| الإتاحة: | https://doi.org/10.1016/j.molcel.2018.07.030Test https://discovery.dundee.ac.uk/en/publications/81b9c4e4-1d77-4814-a958-c40b9483aea7Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.B882F652 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.molcel.2018.07.030 |
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