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Stromal Cell PD-L1 Inhibits CD8+ T-cell Antitumor Immune Responses and Promotes Colon Cancer

Overview of attention for article published in Cancer Immunology Research, September 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (90th percentile)
  • Good Attention Score compared to outputs of the same age and source (72nd percentile)

Mentioned by

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34 tweeters
googleplus
1 Google+ user

Citations

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1 Dimensions

Readers on

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16 Mendeley
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Title
Stromal Cell PD-L1 Inhibits CD8+ T-cell Antitumor Immune Responses and Promotes Colon Cancer
Published in
Cancer Immunology Research, September 2018
DOI 10.1158/2326-6066.cir-17-0443
Pubmed ID
Authors

Grace O'Malley, Oliver Treacy, Kevin Lynch, Serika D. Naicker, Niamh A. Leonard, Paul Lohan, Philip D. Dunne, Thomas Ritter, Laurence J. Egan, Aideen E. Ryan

Abstract

Stromal cells of mesenchymal origin reside below the epithelial compartment and provide structural support in the intestine. These intestinal stromal cells interact with both the epithelial cell compartments, as well as infiltrating hematopoietic immune cells. The importance of these cells in regulating immune homeostasis during inflammation is well recognized. However, little is known about their function and phenotype in the inflammatory tumor microenvironment. Using a syngeneic, immunogenic model of colorectal cancer, we showed that TNFα-initiated inflammatory signaling in CT26 colorectal cancer cells selectively induced PD-L1 expression in stromal cells. Using PD-L1 shRNA and antibody-mediated approaches, we showed that stromal cell PD-L1 potentiated enhanced immunosuppression, characterized by inhibition of activated CD8+ granzyme B-secreting T cells in vitro, and the inhibition of CD8+ effector cells was associated with enhanced tumor progression. Stromal cell immunosuppressive and tumor-promoting effects could be reversed with administration of an anti-PD-1 in vivo. We validated our findings of stromal cell PD-L1 expression in two cohorts of clinical samples and also observed PD-L1 induction on human stromal cells in response to exposure to the inflammatory secretome from human colon cancer cells, irrespective of microsatellite instability. Collectively, our data showed that tumor-associated stromal cells support T-cell suppression by PD-L1 induction, which is dependent on colon cancer inflammatory signaling. Our findings reveal a key role of mesenchymal stromal cell PD-L1 in suppression of CD8+ antitumor immune responses and potentiation of colorectal cancer progression.

Twitter Demographics

The data shown below were collected from the profiles of 34 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 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 31%
Unspecified 3 19%
Student > Ph. D. Student 1 6%
Researcher 1 6%
Student > Doctoral Student 1 6%
Other 1 6%
Unknown 4 25%
Readers by discipline Count As %
Unspecified 4 25%
Medicine and Dentistry 3 19%
Immunology and Microbiology 3 19%
Biochemistry, Genetics and Molecular Biology 1 6%
Pharmacology, Toxicology and Pharmaceutical Science 1 6%
Other 0 0%
Unknown 4 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 22. 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 07 August 2019.
All research outputs
#720,916
of 13,371,296 outputs
Outputs from Cancer Immunology Research
#67
of 810 outputs
Outputs of similar age
#26,153
of 267,425 outputs
Outputs of similar age from Cancer Immunology Research
#10
of 36 outputs
Altmetric has tracked 13,371,296 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 810 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.4. 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 267,425 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 90% of its contemporaries.
We're also able to compare this research output to 36 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 72% of its contemporaries.