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Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy

Overview of attention for article published in Journal for Immunotherapy of Cancer, June 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (94th percentile)

Mentioned by

news
3 news outlets
blogs
1 blog
twitter
36 tweeters

Citations

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140 Dimensions

Readers on

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217 Mendeley
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Title
Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy
Published in
Journal for Immunotherapy of Cancer, June 2018
DOI 10.1186/s40425-018-0371-5
Pubmed ID
Authors

Amber J. Giles, Marsha-Kay N. D. Hutchinson, Heather M. Sonnemann, Jinkyu Jung, Peter E. Fecci, Nivedita M. Ratnam, Wei Zhang, Hua Song, Rolanda Bailey, Dionne Davis, Caitlin M. Reid, Deric M. Park, Mark R. Gilbert

Abstract

Corticosteroids are routinely utilized to alleviate edema in patients with intracranial lesions and are first-line agents to combat immune-related adverse events (irAEs) that arise with immune checkpoint blockade treatment. However, it is not known if or when corticosteroids can be administered without abrogating the efforts of immunotherapy. The purpose of this study was to evaluate the impact of dexamethasone on lymphocyte activation and proliferation during checkpoint blockade to provide guidance for corticosteroid use while immunotherapy is being implemented as a cancer treatment. Lymphocyte proliferation, differentiation, and cytokine production were evaluated during dexamethasone exposure. Human T cells were stimulated through CD3 ligation and co-stimulated either directly by CD28 ligation or by providing CD80, a shared ligand for CD28 and CTLA-4. CTLA-4 signaling was inhibited by antibody blockade using ipilimumab which has been approved for the treatment of several solid tumors. The in vivo effects of dexamethasone during checkpoint blockade were evaluated using the GL261 syngeneic mouse intracranial model, and immune populations were profiled by flow cytometry. Dexamethasone upregulated CTLA-4 mRNA and protein in CD4 and CD8 T cells and blocked CD28-mediated cell cycle entry and differentiation. Naïve T cells were most sensitive, leading to a decrease of the development of more differentiated subsets. Resistance to dexamethasone was conferred by blocking CTLA-4 or providing strong CD28 co-stimulation prior to dexamethasone exposure. CTLA-4 blockade increased IFNγ expression, but not IL-2, in stimulated human peripheral blood T cells exposed to dexamethasone. Finally, we found that CTLA-4 blockade partially rescued T cell numbers in mice bearing intracranial gliomas. CTLA-4 blockade was associated with increased IFNγ-producing tumor-infiltrating T cells and extended survival of dexamethasone-treated mice. Dexamethasone-mediated T cell suppression diminishes naïve T cell proliferation and differentiation by attenuating the CD28 co-stimulatory pathway. However, CTLA-4, but not PD-1 blockade can partially prevent some of the inhibitory effects of dexamethasone on the immune response.

Twitter Demographics

The data shown below were collected from the profiles of 36 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 217 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 217 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 37 17%
Student > Ph. D. Student 31 14%
Student > Master 26 12%
Researcher 22 10%
Other 17 8%
Other 27 12%
Unknown 57 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 39 18%
Medicine and Dentistry 37 17%
Agricultural and Biological Sciences 19 9%
Immunology and Microbiology 16 7%
Pharmacology, Toxicology and Pharmaceutical Science 14 6%
Other 24 11%
Unknown 68 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 47. 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 05 July 2021.
All research outputs
#616,069
of 19,410,335 outputs
Outputs from Journal for Immunotherapy of Cancer
#129
of 2,213 outputs
Outputs of similar age
#16,791
of 292,841 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#1
of 1 outputs
Altmetric has tracked 19,410,335 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,213 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.1. This one has done particularly well, scoring higher than 94% 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 292,841 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 94% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them