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Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy

Overview of attention for article published in Journal of Clinical Investigation, July 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 (95th percentile)
  • Good Attention Score compared to outputs of the same age and source (78th percentile)

Mentioned by

news
7 news outlets
blogs
1 blog
twitter
19 tweeters
facebook
6 Facebook pages

Citations

dimensions_citation
113 Dimensions

Readers on

mendeley
115 Mendeley
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Title
Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy
Published in
Journal of Clinical Investigation, July 2017
DOI 10.1172/jci93182
Pubmed ID
Authors

Keehoon Jung, Takahiro Heishi, Omar F. Khan, Piotr S. Kowalski, Joao Incio, Nuh N. Rahbari, Euiheon Chung, Jeffrey W. Clark, Christopher G. Willett, Andrew D. Luster, Seok Hyun Yun, Robert Langer, Daniel G. Anderson, Timothy P. Padera, Rakesh K. Jain, Dai Fukumura

Abstract

Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated in both human and murine tumors following VEGF signaling blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial cells in vitro. Intravital microscopy revealed that CX3CR1 is critical for Ly6Clo monocyte transmigration across the endothelium in murine CRC tumors. Moreover, Ly6Clo monocytes recruit Ly6G+ neutrophils via CXCL5 and produce IL-10, which inhibits adaptive immunity. Preventing Ly6Clo monocyte or Ly6G+ neutrophil infiltration into tumors enhanced inhibition of tumor growth with anti-VEGFR2 therapy. Furthermore, a gene therapy using a nanoparticle formulated with an siRNA against CX3CL1 reduced Ly6Clo monocyte recruitment and improved outcome of anti-VEGFR2 therapy in mouse CRCs. Our study unveils an immunosuppressive function of Ly6Clo monocytes that, to our knowledge, has yet to be reported in any context. We also reveal molecular mechanisms underlying antiangiogenic treatment resistance, suggesting potential immunomodulatory strategies to enhance the long-term clinical outcome of anti-VEGF therapies.

Twitter Demographics

The data shown below were collected from the profiles of 19 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 115 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 115 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 31 27%
Researcher 20 17%
Other 9 8%
Student > Master 8 7%
Student > Bachelor 6 5%
Other 19 17%
Unknown 22 19%
Readers by discipline Count As %
Medicine and Dentistry 27 23%
Biochemistry, Genetics and Molecular Biology 18 16%
Immunology and Microbiology 18 16%
Agricultural and Biological Sciences 10 9%
Engineering 6 5%
Other 10 9%
Unknown 26 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 67. 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 03 July 2018.
All research outputs
#542,051
of 22,952,268 outputs
Outputs from Journal of Clinical Investigation
#645
of 16,405 outputs
Outputs of similar age
#12,747
of 312,375 outputs
Outputs of similar age from Journal of Clinical Investigation
#20
of 89 outputs
Altmetric has tracked 22,952,268 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 16,405 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.6. This one has done particularly well, scoring higher than 96% 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 312,375 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 95% of its contemporaries.
We're also able to compare this research output to 89 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.