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Targeting the IL1β Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses

Overview of attention for article published in Cancer Immunology Research, April 2023
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About this Attention Score

  • 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
Targeting the IL1β Pathway for Cancer Immunotherapy Remodels the Tumor Microenvironment and Enhances Antitumor Immune Responses
Published in
Cancer Immunology Research, April 2023
DOI 10.1158/2326-6066.cir-22-0290
Pubmed ID
Authors

Rohan Diwanji, Neil A. O'Brien, Jiyoung E. Choi, Beverly Nguyen, Tyler Laszewski, Angelo L. Grauel, Zheng Yan, Xin Xu, Jincheng Wu, David A. Ruddy, Michelle Piquet, Marc R. Pelletier, Alexander Savchenko, LaSalette Charette, Vanessa Rodrik-Outmezguine, Jason Baum, John M. Millholland, Connie C. Wong, Anne-Marie Martin, Glenn Dranoff, Iulian Pruteanu-Malinici, Viviana Cremasco, Catherine Sabatos-Peyton, Pushpa Jayaraman

Abstract

High levels of IL-1β can result in chronic inflammation, which in turn can promote tumor growth and metastasis. Inhibition of IL-1β could therefore be a promising therapeutic option in the treatment of cancer. Here, the effects of IL-1β blockade induced by the monoclonal antibodies canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti-PD-1, anti-VEGFα and anti-TGFβ treatment in syngeneic and humanized mouse models of cancers of different origin. Canakinumab and gevokizumab did not show notable efficacy as single-agent therapies; however, IL-1β blockade enhanced the effectiveness of docetaxel and anti-PD-1. Accompanying these effects, blockade of IL-1β alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells and effector T cells. Further investigation revealed that cancer-associated fibroblasts (CAFs) were the cell type most affected by treatment with canakinumab or gevokizumab in terms of change in gene expression. IL-1β inhibition drove phenotypic changes in CAF populations, particularly those with the ability to influence immune cell recruitment. These results suggest that the observed remodeling of the TME following IL-1β blockade may stem from changes in CAF populations. Overall, the results presented here support the potential use of IL-1β inhibition in cancer treatment. Further exploration in ongoing clinical studies will help identify the best combination partners for different cancer types, cancer stages and lines of treatment.

Twitter Demographics

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Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 20 May 2023.
All research outputs
#5,750,077
of 23,926,844 outputs
Outputs from Cancer Immunology Research
#597
of 1,438 outputs
Outputs of similar age
#94,448
of 408,721 outputs
Outputs of similar age from Cancer Immunology Research
#15
of 27 outputs
Altmetric has tracked 23,926,844 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.0. This one has gotten more attention than average, scoring higher than 58% 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 408,721 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 27 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.