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Entinostat Decreases Immune Suppression to Promote Antitumor Responses in a HER2+ Breast Tumor Microenvironment

Overview of attention for article published in Cancer Immunology Research, February 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 (84th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

Mentioned by

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16 tweeters

Citations

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2 Dimensions

Readers on

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11 Mendeley
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Title
Entinostat Decreases Immune Suppression to Promote Antitumor Responses in a HER2+ Breast Tumor Microenvironment
Published in
Cancer Immunology Research, February 2022
DOI 10.1158/2326-6066.cir-21-0170
Pubmed ID
Authors

Dimitrios N. Sidiropoulos, Christine I. Rafie, Julie K. Jang, Sofi Castanon, Aaron G. Baugh, Edgar Gonzalez, Brian J. Christmas, Valerie H. Narumi, Emily F. Davis-Marcisak, Gaurav Sharma, Emma Bigelow, Ajay Vaghasia, Anuj Gupta, Alyza Skaist, Michael Considine, Sarah J. Wheelan, Sathish Kumar Ganesan, Min Yu, Srinivasan Yegnasubramanian, Vered Stearns, Roisin M. Connolly, Daria A. Gaykalova, Luciane T. Kagohara, Elizabeth M. Jaffee, Elana J. Fertig, Evanthia T. Roussos Torres

Abstract

Therapeutic combinations to alter immunosuppressive, solid tumor microenvironments (TMEs), such as in breast cancer, are essential to improve responses to immune checkpoint inhibitors (ICIs). Entinostat, an oral histone deacetylase inhibitor (HDACi), has been shown to improve responses to ICIs in various tumor models with immunosuppressive TMEs. The precise and comprehensive alterations to the TME induced by entinostat remain unknown. Here, we employed single-cell RNA-sequencing on HER2-overexpressing breast tumors from mice treated with entinostat and ICIs in order to fully characterize changes across multiple cell types within the TME. This analysis demonstrates that treatment with entinostat induced a shift from a pro-tumor to an anti-tumor TME signature, characterized predominantly by changes in myeloid cells. We confirmed myeloid-derived suppressor cells (MDSCs) within entinostat-treated tumors associated with a less suppressive granulocytic (G)-MDSC phenotype and exhibited altered suppressive signaling that involved the NFkB and STAT3 pathways. In addition to MDSCs, tumor-associated macrophages were epigenetically reprogrammed from a pro-tumor M2-like phenotype toward an anti-tumor M1-like phenotype, which may be contributing to a more sensitized TME. Overall, our in-depth analysis suggests that entinostat-induced changes on multiple myeloid cell types reduce immunosuppression and increase anti-tumor responses, which, in turn, improve sensitivity to ICIs. Sensitization of the TME by entinostat could ultimately broaden the population of patients with breast cancer who could benefit from ICIs.

Twitter Demographics

The data shown below were collected from the profiles of 16 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 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 27%
Professor 2 18%
Student > Ph. D. Student 1 9%
Unknown 5 45%
Readers by discipline Count As %
Medicine and Dentistry 3 27%
Immunology and Microbiology 1 9%
Unknown 7 64%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 18 May 2022.
All research outputs
#2,435,980
of 21,370,427 outputs
Outputs from Cancer Immunology Research
#247
of 1,273 outputs
Outputs of similar age
#51,016
of 336,271 outputs
Outputs of similar age from Cancer Immunology Research
#4
of 33 outputs
Altmetric has tracked 21,370,427 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,273 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.7. This one has done well, scoring higher than 80% 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 336,271 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 84% of its contemporaries.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.