Abstract：
:Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction plays a crucial role in tumor-associated immune escape. Here, we verify that triple-negative breast cancer (TNBC) has higher PD-L1 expression than other subtypes. We then discover that nucleophosmin (NPM1) binds to PD-L1 promoter specifically in TNBC cells and activates PD-L1 transcription, thus inhibiting T cell activity in vitro and in vivo. Furthermore, we demonstrate that PARP1 suppresses PD-L1 transcription through its interaction with the nucleic acid binding domain of NPM1, which is required for the binding of NPM1 at PD-L1 promoter. Consistently, the PARP1 inhibitor olaparib elevates PD-L1 expression in TNBC and exerts a better effect with anti-PD-L1 therapy. Together, our research has revealed NPM1 as a transcription regulator of PD-L1 in TNBC, which could lead to potential therapeutic strategies to enhance the efficacy of cancer immunotherapy.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Qin G,Wang X,Ye S,Li Y,Chen M,Wang S,Qin T,Zhang C,Li Y,Long Q,Hu H,Shi D,Li J,Zhang K,Zhai Q,Tang Y,Kang T,Lan P,Xie F,Lu J,Deng Wdoi
10.1038/s41467-020-15364-zsubject
Has Abstractpub_date
2020-04-03 00:00:00pages
1669issue
1issn
2041-1723pii
10.1038/s41467-020-15364-zjournal_volume
11pub_type
杂志文章abstract：:TH17 cells exemplify environmental immune adaptation: they can acquire both a pathogenic and an anti-inflammatory fate. However, it is not known whether the anti-inflammatory fate is merely a vestigial trait, or whether it serves to preserve the integrity of the host tissues. Here we show that the capacity of TH17 cel...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-020-17097-5
更新日期：2020-07-03 00:00:00
abstract：:Sphingosine-1-phosphate (S1P) participates in inflammation; however, its role in leukocyte rolling is still unclear. Here we use intravital microscopy in inflamed mouse cremaster muscle venules and human endothelial cells to show that S1P contributes to P-selectin-dependent leukocyte rolling through endothelial S1P re...
journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms7416
更新日期：2015-04-02 00:00:00
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journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-018-04601-1
更新日期：2018-06-05 00:00:00
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journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/s41467-017-02031-z
更新日期：2017-12-07 00:00:00
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pub_type： 杂志文章
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更新日期：2010-08-10 00:00:00
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journal_title：Nature communications
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更新日期：2012-01-01 00:00:00
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journal_title：Nature communications
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更新日期：2019-06-13 00:00:00
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更新日期：2017-12-20 00:00:00
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更新日期：2019-07-11 00:00:00
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journal_title：Nature communications
pub_type： 杂志文章
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更新日期：2012-07-03 00:00:00
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更新日期：2016-08-25 00:00:00
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pub_type： 杂志文章
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更新日期：2017-06-08 00:00:00
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journal_title：Nature communications
pub_type： 杂志文章
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更新日期：2013-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/ncomms12829
更新日期：2016-09-09 00:00:00
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pub_type： 杂志文章
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更新日期：2017-07-03 00:00:00
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pub_type： 杂志文章
doi：10.1038/ncomms3297
更新日期：2013-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/s41467-020-14689-z
更新日期：2020-02-13 00:00:00
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journal_title：Nature communications
pub_type： 杂志文章
doi：10.1038/ncomms11216
更新日期：2016-04-06 00:00:00
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doi：10.1038/ncomms7853
更新日期：2015-04-22 00:00:00
abstract：:It has previously been postulated that the Earth's hydrous mantle transition zone may play a key role in intraplate magmatism, but no confirmatory evidence has been reported. Here we demonstrate that hydrothermally altered subducted oceanic crust was involved in generating the late Cenozoic Chifeng continental flood b...
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更新日期：2015-07-14 00:00:00
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更新日期：2017-10-31 00:00:00
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更新日期：2019-07-04 00:00:00
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更新日期：2014-04-02 00:00:00
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更新日期：2018-09-28 00:00:00
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doi：10.1038/ncomms13869
更新日期：2016-12-13 00:00:00
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更新日期：2020-12-09 00:00:00
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更新日期：2021-01-22 00:00:00
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更新日期：2015-01-20 00:00:00
