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TGFβ and CIS Inhibition Overcomes NK-cell Suppression to Restore Antitumor Immunity

Overview of attention for article published in Cancer Immunology Research, July 2022
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (76th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
TGFβ and CIS Inhibition Overcomes NK-cell Suppression to Restore Antitumor Immunity
Published in
Cancer Immunology Research, July 2022
DOI 10.1158/2326-6066.cir-21-1052
Pubmed ID
Authors

Fernando Souza-Fonseca-Guimaraes, Gustavo R. Rossi, Laura F. Dagley, Momeneh Foroutan, Timothy R. McCulloch, Jumana Yousef, Hae-Young Park, Jennifer H. Gunter, Paul A. Beavis, Cheng-Yu Lin, Soroor Hediyeh-Zadeh, Tania Camilleri, Melissa J. Davis, Nicholas D. Huntington

Abstract

Antibodies targeting "immune checkpoints" have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8+ T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation. NK cell anti-tumor function is dependent on the cytokine interleukin (IL)-15. Ablation of the IL-15 signaling inhibitor CIS (Cish) enhances NK cell anti-tumor immunity by increasing NK cell metabolism and persistence within the tumor microenvironment (TME). The TME has also been shown to impair NK cell fitness via the production of immunosuppressive TGF-β, a suppression which occurs even in the presence of high IL-15 signaling. Here, we identified an unexpected interaction between CIS and the TGF-β signaling pathway in NK cells. Independently, Cish- and Tgfbr2-deficient NK cells are both hyper-responsive to IL-15 and hypo-responsive to TGF-β, with dramatically enhanced anti-tumor immunity. Remarkably, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development, suggesting that combining suppression of these two pathways might represent a novel therapeutic strategy to enhance innate anti-cancer immunity.

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Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 29 June 2022.
All research outputs
#4,211,410
of 21,682,700 outputs
Outputs from Cancer Immunology Research
#444
of 1,336 outputs
Outputs of similar age
#65,188
of 281,464 outputs
Outputs of similar age from Cancer Immunology Research
#12
of 21 outputs
Altmetric has tracked 21,682,700 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,336 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.4. This one has gotten more attention than average, scoring higher than 66% 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 281,464 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.