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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
62 tweeters
patent
1 patent

Citations

dimensions_citation
100 Dimensions

Readers on

mendeley
119 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.

Twitter Demographics

The data shown below were collected from the profiles of 62 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 119 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 116 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 30 25%
Researcher 26 22%
Student > Master 11 9%
Student > Postgraduate 8 7%
Professor 6 5%
Other 17 14%
Unknown 21 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 39 33%
Agricultural and Biological Sciences 22 18%
Medicine and Dentistry 20 17%
Chemistry 5 4%
Immunology and Microbiology 5 4%
Other 3 3%
Unknown 25 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 77. 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 20 March 2020.
All research outputs
#296,083
of 16,064,848 outputs
Outputs from Cell Reports
#652
of 7,965 outputs
Outputs of similar age
#9,642
of 263,068 outputs
Outputs of similar age from Cell Reports
#22
of 231 outputs
Altmetric has tracked 16,064,848 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 7,965 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.2. 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 263,068 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 231 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.