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Interleukin-27 signaling serves as an immunological checkpoint for innate cytotoxic cells to promote hepatocellular carcinoma

Overview of attention for article published in Cancer Discovery, June 2022
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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 (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (81st percentile)

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1 news outlet
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33 tweeters
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Title
Interleukin-27 signaling serves as an immunological checkpoint for innate cytotoxic cells to promote hepatocellular carcinoma
Published in
Cancer Discovery, June 2022
DOI 10.1158/2159-8290.cd-20-1628
Pubmed ID
Authors

Aghayev, Turan, Mazitova, Aleksandra M., Fang, Jennifer R., Peshkova, Iuliia O., Rausch, Matthew, Hung, Manhsin, White, Kerry F., Masia, Ricard, Titerina, Elizaveta K., Fatkhullina, Aliia R., Cousineau, Isabelle, Turcotte, Simon, Zhigarev, Dmitry, Marchenko, Anastasiia, Khoziainova, Svetlana, Makhov, Petr, Tan, Yin Fei, Kossenkov, Andrew V., Wiest, David L., Stagg, John, Wang, Xin Wei, Campbell, Kerry S., Dzutsev, Amiran K., Trinchieri, Giorgio, Hill, Jonathan A., Grivennikov, Sergei I., Koltsova, Ekaterina K., Mazitova, Aleksandra M, Fang, Jennifer R, Peshkova, Iuliia O, White, Kerry F, Titerina, Elizaveta K, Fatkhullina, Aliia R, Kossenkov, Andrew V, Wiest, David L, Campbell, Kerry S, Dzutsev, Amiran K, Hill, Jonathan A, Grivennikov, Sergei I, Koltsova, Ekaterina K

Abstract

While inflammatory mechanisms driving hepatocellular carcinoma (HCC) had been proposed, the regulators of anti-cancer immunity in HCC remain poorly understood. We found that IL-27 receptor (IL-27R) signaling promotes HCC development in vivo. High IL-27EBI3 cytokine or IL-27RA expression correlated with poor prognosis for patients with HCC. Loss of IL-27R suppressed HCC in vivo in two different models of hepatocarcinogenesis. Mechanistically, IL-27R signaling within the tumor microenvironment restrains the cytotoxicity of innate cytotoxic lymphocytes. IL-27R ablation enhanced their accumulation and activation, while depletion or functional impairment of innate cytotoxic cells abrogated the effect of IL-27R disruption. Pharmacological neutralization of IL-27 signaling increased infiltration of innate cytotoxic lymphocytes with upregulated cytotoxic molecules and reduced HCC development. Our data reveal an unexpected role of IL-27R signaling as an immunological checkpoint regulating innate cytotoxic lymphocytes and promoting HCC of different etiologies, thus indicating a therapeutic potential for IL-27 pathway blockade in HCC.

Twitter Demographics

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Attention Score in Context

This research output has an Altmetric Attention Score of 27. 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 26 June 2022.
All research outputs
#1,113,523
of 21,421,530 outputs
Outputs from Cancer Discovery
#525
of 3,428 outputs
Outputs of similar age
#11,459
of 180,033 outputs
Outputs of similar age from Cancer Discovery
#9
of 44 outputs
Altmetric has tracked 21,421,530 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 3,428 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.3. This one has done well, scoring higher than 84% 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 180,033 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 93% of its contemporaries.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 81% of its contemporaries.