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The Impact of Macrophage- and Microglia-Secreted TNFα on Oncolytic HSV-1 Therapy in the Glioblastoma Tumor Microenvironment

Overview of attention for article published in Clinical Cancer Research, July 2015
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  • Above-average Attention Score compared to outputs of the same age (52nd percentile)
  • Average Attention Score compared to outputs of the same age and source

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2 X users
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1 peer review site

Citations

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72 Dimensions

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93 Mendeley
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Title
The Impact of Macrophage- and Microglia-Secreted TNFα on Oncolytic HSV-1 Therapy in the Glioblastoma Tumor Microenvironment
Published in
Clinical Cancer Research, July 2015
DOI 10.1158/1078-0432.ccr-14-3118
Pubmed ID
Authors

W. Hans Meisen, Eric S. Wohleb, Alena Cristina Jaime-Ramirez, Chelsea Bolyard, Ji Young Yoo, Luke Russell, Jayson Hardcastle, Samuel Dubin, Kamaldeen Muili, Jianhua Yu, Michael Caligiuri, Jonathan Godbout, Balveen Kaur

Abstract

Oncolytic herpes simplex viruses [oHSV] represent a promising therapy for glioblastoma [GB], but their clinical success has been limited. Early innate immune responses to viral infection reduce oHSV replication, tumor destruction, and efficacy. Here, we characterized the antiviral effects of macrophages and microglia on viral therapy for GB. Quantitative flow cytometry of mice with intracranial gliomas [± oHSV] was utilized to examine macrophage/ microglia infiltration and activation. In vitro co-culture assays of infected glioma cells with microglia/macrophages were utilized to test their impact on oHSV replication. Macrophages from TNFα knockout mice and blocking antibodies were used to evaluate the biological effects of TNFα on virus replication. TNFα blocking antibodies were utilized to evaluate the impact of TNFα on oHSV therapy in vivo. Flow cytometry analysis revealed a 7.9 fold increase in macrophage infiltration after virus treatment. Tumor infiltrating macrophages/microglia were polarized towards a M1, pro-inflammatory phenotype and they expressed high levels of CD86, MHCII, and Ly6C. Macrophages/microglia produced significant amounts of TNFα in response to infected glioma cells in vitro and in vivo. Utilizing TNFα blocking antibodies and macrophages derived from TNFα knockout mice we discovered TNFα induced apoptosis in infected tumor cells and inhibited virus replication. Finally, we demonstrated the transient blockade of TNFα from the tumor microenvironment with TNFα blocking antibodies significantly enhanced virus replication and survival in GB intracranial tumors. The results of these studies suggest FDA approved TNFα inhibitors may significantly improve the efficacy of oncolytic virus therapy.

X Demographics

X Demographics

The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 2 2%
United States 1 1%
Brazil 1 1%
Unknown 89 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 21 23%
Student > Master 11 12%
Researcher 10 11%
Student > Bachelor 9 10%
Unspecified 8 9%
Other 20 22%
Unknown 14 15%
Readers by discipline Count As %
Medicine and Dentistry 16 17%
Biochemistry, Genetics and Molecular Biology 15 16%
Agricultural and Biological Sciences 10 11%
Neuroscience 10 11%
Immunology and Microbiology 9 10%
Other 17 18%
Unknown 16 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 17 March 2017.
All research outputs
#13,356,007
of 22,797,621 outputs
Outputs from Clinical Cancer Research
#9,432
of 12,588 outputs
Outputs of similar age
#122,585
of 262,637 outputs
Outputs of similar age from Clinical Cancer Research
#103
of 175 outputs
Altmetric has tracked 22,797,621 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 12,588 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.8. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
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 262,637 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 175 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.