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BRAF inhibitors stimulate inflammasome activation and interleukin 1 beta production in dendritic cells

Overview of attention for article published in Oncotarget, June 2018
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  • Good Attention Score compared to outputs of the same age and source (71st percentile)

Mentioned by

twitter
3 tweeters

Citations

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34 Dimensions

Readers on

mendeley
27 Mendeley
Title
BRAF inhibitors stimulate inflammasome activation and interleukin 1 beta production in dendritic cells
Published in
Oncotarget, June 2018
DOI 10.18632/oncotarget.25511
Pubmed ID
Authors

Eva Hajek, Franziska Krebs, Rebekka Bent, Katharina Haas, Antje Bast, Ivo Steinmetz, Andrea Tuettenberg, Stephan Grabbe, Matthias Bros

Abstract

Melanoma is the most dangerous form of skin cancer with a growing incidence over the last decades. Fourty percent of all melanomas harbor a mutation in the signaling adaptor BRAF (V600E) that results in ERK hyperactivity as an oncogenic driver. In these cases, treatment with the BRAFV600E inhibitors Vemurafenib (VEM) or Dabrafenib (DAB) coapplied with the MEK1/2 inhibitors Cobimetinib (COB) or Trametinib (TRA) can result in long-term suppression of tumor growth. Besides direct suppression of ERK activity, these inhibitors have been reported to also modulate tumor immune responses, and exert pro-inflammatory side effects such as fever and rash in some patients. Here we asked for potential effects of BRAFV600E inhibitors on dendritic cells (DC) which are essential for the induction of adaptive anti-tumor responses. Both splenic and bone marrow-derived (BM) mouse dendritic cells (DC) up-regulated costimulator expression (CD80, CD86) in response to DAB but not VEM treatment. Moreover, DAB and to lesser extent VEM enhanced IL-1β (interleukin 1 beta) release by splenic DC, and by LPS-stimulated BMDC. We demonstrate that DAB and VEM activated the NLRC4/Caspase-1 inflammasome. At high concentration, DAB also induced inflammasome activation independent of Caspase-1. TRA and COB elevated MHCII expression on BMDC, and modulated the LPS-induced cytokine pattern. Immunomodulatory activity of DAB and VEM was also observed in human monocyte-derived DC, and DAB induced IL-1β in human primary DC. Altogether, our study shows that BRAFV600E inhibitors upregulate IL-1β release by mouse and human DC which may affect the DC-mediated course of anti-tumor immune responses.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 5 19%
Student > Bachelor 3 11%
Student > Ph. D. Student 3 11%
Student > Master 3 11%
Other 2 7%
Other 5 19%
Unknown 6 22%
Readers by discipline Count As %
Medicine and Dentistry 8 30%
Biochemistry, Genetics and Molecular Biology 5 19%
Immunology and Microbiology 5 19%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Materials Science 1 4%
Other 0 0%
Unknown 7 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 10 July 2018.
All research outputs
#7,608,285
of 13,205,256 outputs
Outputs from Oncotarget
#2,696
of 12,007 outputs
Outputs of similar age
#137,463
of 266,916 outputs
Outputs of similar age from Oncotarget
#56
of 224 outputs
Altmetric has tracked 13,205,256 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,007 research outputs from this source. They receive a mean Attention Score of 3.8. This one has gotten more attention than average, scoring higher than 73% 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 266,916 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 224 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.