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BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1

Overview of attention for article published in Cell Reports, February 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

Mentioned by

news
5 news outlets
twitter
56 X users
patent
6 patents
wikipedia
1 Wikipedia page

Citations

dimensions_citation
237 Dimensions

Readers on

mendeley
176 Mendeley
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Title
BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1
Published in
Cell Reports, February 2017
DOI 10.1016/j.celrep.2017.02.011
Pubmed ID
Authors

Simon J. Hogg, Stephin J. Vervoort, Sumit Deswal, Christopher J. Ott, Jason Li, Leonie A. Cluse, Paul A. Beavis, Phillip K. Darcy, Benjamin P. Martin, Andrew Spencer, Anna K. Traunbauer, Irina Sadovnik, Karin Bauer, Peter Valent, James E. Bradner, Johannes Zuber, Jake Shortt, Ricky W. Johnstone

Abstract

BET inhibitors (BETi) target bromodomain-containing proteins and are currently being evaluated as anti-cancer agents. We find that maximal therapeutic effects of BETi in a Myc-driven B cell lymphoma model required an intact host immune system. Genome-wide analysis of the BETi-induced transcriptional response identified the immune checkpoint ligand Cd274 (Pd-l1) as a Myc-independent, BETi target-gene. BETi directly repressed constitutively expressed and interferon-gamma (IFN-γ) induced CD274 expression across different human and mouse tumor cell lines and primary patient samples. Mechanistically, BETi decreased Brd4 occupancy at the Cd274 locus without any change in Myc occupancy, resulting in transcriptional pausing and rapid loss of Cd274 mRNA production. Finally, targeted inhibition of the PD-1/PD-L1 axis by combining anti-PD-1 antibodies and the BETi JQ1 caused synergistic responses in mice bearing Myc-driven lymphomas. Our data uncover an interaction between BETi and the PD-1/PD-L1 immune-checkpoint and provide mechanistic insight into the transcriptional regulation of CD274.

X Demographics

X Demographics

The data shown below were collected from the profiles of 56 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 176 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
United States 1 <1%
France 1 <1%
Unknown 173 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 38 22%
Researcher 29 16%
Student > Master 15 9%
Student > Bachelor 10 6%
Other 9 5%
Other 25 14%
Unknown 50 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 46 26%
Medicine and Dentistry 31 18%
Agricultural and Biological Sciences 24 14%
Chemistry 7 4%
Immunology and Microbiology 5 3%
Other 7 4%
Unknown 56 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 78. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 February 2023.
All research outputs
#550,019
of 25,418,993 outputs
Outputs from Cell Reports
#1,135
of 13,001 outputs
Outputs of similar age
#11,599
of 324,201 outputs
Outputs of similar age from Cell Reports
#22
of 241 outputs
Altmetric has tracked 25,418,993 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 13,001 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 30.3. This one has done particularly well, scoring higher than 91% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 324,201 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 241 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.