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DOI | 10.1126/science.aav7062 |
Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses | |
Sugiura, Daisuke1; Maruhashi, Takumi1; Okazaki, Il-mi1; Shimizu, Kenji1; Maeda, Takeo K.1; Takemoto, Tatsuya2; Okazaki, Taku1 | |
2019-05-10 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6440页码:558-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Japan |
英文摘要 | Targeted blockade of PD-1 with immune checkpoint inhibitors can activate Tcells to destroy tumors. PD-1 is believed to function mainly at the effector, but not in the activation, phase of Tcell responses, yet how PD-1 function is restricted at the activation stage is currently unknown. Here we demonstrate that CD80 interacts with PD-L1 in cis on antigen-presenting cells (APCs) to disrupt PD-L1/PD-1 binding. Subsequently, PD-L1 cannot engage PD-1 to inhibit Tcell activation when APCs express substantial amounts of CD80. In knock-in mice in which cis-PD-L1/CD80 interactions do not occur, tumor immunity and autoimmune responses were greatly attenuated by PD-1. These findings indicate that CD80 on APCs limits the PD-1 coinhibitory signal, while promoting CD28-mediated costimulation, and highlight critical components for induction of optimal immune responses. |
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:000467631800037 |
WOS关键词 | CRYSTAL-STRUCTURE ; ANTI-PD-L1 ANTIBODY ; RECEPTOR ; SUPPRESSION ; ACTIVATION ; EXPRESSION ; INDUCTION ; MPDL3280A ; LIGANDS ; COMPLEX |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
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/201395 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Tokushima Univ, Inst Adv Med Sci, Div Immune Regulat, 3-18-15 Kuramoto, Tokushima 7708503, Japan; 2.Tokushima Univ, Inst Adv Med Sci, Lab Embryol, 3-18-15 Kuramoto, Tokushima 7708503, Japan |
推荐引用方式 GB/T 7714 | Sugiura, Daisuke,Maruhashi, Takumi,Okazaki, Il-mi,et al. Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses[J]. SCIENCE,2019,364(6440):558-+. |
APA | Sugiura, Daisuke.,Maruhashi, Takumi.,Okazaki, Il-mi.,Shimizu, Kenji.,Maeda, Takeo K..,...&Okazaki, Taku.(2019).Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses.SCIENCE,364(6440),558-+. |
MLA | Sugiura, Daisuke,et al."Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses".SCIENCE 364.6440(2019):558-+. |
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