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Phosphatidylserine-targeting antibodies augment the anti-tumorigenic activity of anti-PD-1 therapy by enhancing immune activation and downregulating pro-oncogenic factors induced by T-cell checkpoint…

Overview of attention for article published in Breast Cancer Research, May 2016
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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 (80th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (55th percentile)

Mentioned by

twitter
7 tweeters
patent
2 patents

Citations

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41 Dimensions

Readers on

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116 Mendeley
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Title
Phosphatidylserine-targeting antibodies augment the anti-tumorigenic activity of anti-PD-1 therapy by enhancing immune activation and downregulating pro-oncogenic factors induced by T-cell checkpoint inhibition in murine triple-negative breast cancers
Published in
Breast Cancer Research, May 2016
DOI 10.1186/s13058-016-0708-2
Pubmed ID
Authors

Michael J. Gray, Jian Gong, Michaela M. S. Hatch, Van Nguyen, Christopher C. W. Hughes, Jeff T. Hutchins, Bruce D. Freimark

Abstract

The purpose of this study was to investigate the potential of antibody-directed immunotherapy targeting the aminophospholipid phosphatidylserine, which promotes immunosuppression when exposed in the tumor microenvironment, alone and in combination with antibody treatment towards the T-cell checkpoint inhibitor PD-1 in breast carcinomas, including triple-negative breast cancers. Immune-competent mice bearing syngeneic EMT-6 or E0771 tumors were subjected to treatments comprising of a phosphatidylserine-targeting and an anti-PD-1 antibody either as single or combinational treatments. Anti-tumor effects were determined by tumor growth inhibition and changes in overall survival accompanying each treatment. The generation of a tumor-specific immune response in animals undergoing complete tumor regression was assessed by secondary tumor cell challenge and splenocyte-produced IFNγ in the presence or absence of irradiated tumor cells. Changes in the presence of tumor-infiltrating lymphocytes were assessed by flow cytometry, while mRNA-based immune profiling was determined using NanoString PanCancer Immune Profiling Panel analysis. Treatment by a phosphatidylserine-targeting antibody inhibits in-vivo growth and significantly enhances the anti-tumor activity of antibody-mediated PD-1 therapy, including providing a distinct survival advantage over treatment by either single agent. Animals in which complete tumor regression occurred with combination treatments were resistant to secondary tumor challenge and presented heightened expression levels of splenocyte-produced IFNγ. Combinational treatment by a phosphatidylserine-targeting antibody with anti-PD-1 therapy increased the number of tumor-infiltrating lymphocytes more than that observed with single-arm therapies. Finally, immunoprofiling analysis revealed that the combination of anti-phosphatidylserine targeting antibody and anti-PD-1 therapy enhanced tumor-infiltrating lymphocytes, and increased expression of pro-immunosurveillance-associated cytokines while significantly decreasing expression of pro-tumorigenic cytokines that were induced by single anti-PD-1 therapy. Our data suggest that antibody therapy targeting phosphatidylserine-associated immunosuppression, which has activity as a single agent, can significantly enhance immunotherapies targeting the PD-1 pathway in murine breast neoplasms, including triple-negative breast cancers.

Twitter Demographics

The data shown below were collected from the profiles of 7 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 116 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 <1%
United States 1 <1%
Unknown 114 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 28 24%
Student > Ph. D. Student 25 22%
Student > Doctoral Student 12 10%
Student > Bachelor 11 9%
Student > Master 9 8%
Other 12 10%
Unknown 19 16%
Readers by discipline Count As %
Medicine and Dentistry 23 20%
Biochemistry, Genetics and Molecular Biology 23 20%
Immunology and Microbiology 18 16%
Agricultural and Biological Sciences 14 12%
Pharmacology, Toxicology and Pharmaceutical Science 6 5%
Other 14 12%
Unknown 18 16%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 11 October 2018.
All research outputs
#2,892,906
of 17,360,236 outputs
Outputs from Breast Cancer Research
#396
of 1,706 outputs
Outputs of similar age
#53,890
of 270,179 outputs
Outputs of similar age from Breast Cancer Research
#5
of 9 outputs
Altmetric has tracked 17,360,236 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,706 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.3. This one has done well, scoring higher than 76% 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 270,179 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 80% of its contemporaries.
We're also able to compare this research output to 9 others from the same source and published within six weeks on either side of this one. This one has scored higher than 4 of them.