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DOI | 10.1126/science.aaf1292 |
T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition | |
Hui, Enfu1,2,5; Cheung, Jeanne3; Zhu, Jing3; Su, Xiaolei1,2; Taylor, Marcus J.1,2; Wallweber, Heidi A.3; Sasmal, Dibyendu K.4; Huang, Jun4; Kim, Jeong M.3; Mellman, Ira3; Vale, Ronald D.1,2 | |
2017-03-31 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 355期号:6332页码:1428-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1-recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti-PD-L1/PD-1 therapy. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000397809500044 |
WOS关键词 | CANCER-IMMUNOTHERAPY ; PD-1 EXPRESSION ; ACTIVATION ; EXHAUSTION ; KINASE ; ANTI-PD-1 ; RESPONSES ; SAFETY ; MICROCLUSTERS ; STIMULATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/195736 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA; 2.Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA; 3.Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 USA; 4.Univ Chicago, Inst Mol Engn, Chicago, IL 60637 USA; 5.Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA |
推荐引用方式 GB/T 7714 | Hui, Enfu,Cheung, Jeanne,Zhu, Jing,et al. T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition[J]. SCIENCE,2017,355(6332):1428-+. |
APA | Hui, Enfu.,Cheung, Jeanne.,Zhu, Jing.,Su, Xiaolei.,Taylor, Marcus J..,...&Vale, Ronald D..(2017).T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition.SCIENCE,355(6332),1428-+. |
MLA | Hui, Enfu,et al."T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition".SCIENCE 355.6332(2017):1428-+. |
条目包含的文件 | 条目无相关文件。 |
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