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GITR ligand fusion protein agonist enhances the tumor antigen–specific CD8 T-cell response and leads to long-lasting memory

Overview of attention for article published in Journal for Immunotherapy of Cancer, June 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)

Mentioned by

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20 tweeters

Citations

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18 Dimensions

Readers on

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39 Mendeley
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Title
GITR ligand fusion protein agonist enhances the tumor antigen–specific CD8 T-cell response and leads to long-lasting memory
Published in
Journal for Immunotherapy of Cancer, June 2017
DOI 10.1186/s40425-017-0247-0
Pubmed ID
Authors

Nick M. Durham, Nick Holoweckyj, Randall S. MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H. Robbins

Abstract

The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations. We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy. In TC-1, GITRL-FP was also combined with concurrent administration of an E7-SLP vaccine. We evaluated tumor growth inhibition by tumor volume measurements as well as changes in CD8 T cell populations and function including cytokine production using flow cytometry. Additionally, we interrogated how these therapies resulted in tumor antigen-specific responses using MHC-I dextramer staining and antigen-specific restimulations. In this study, we demonstrate that a GITR ligand fusion protein (GITRL-FP) is an effective modulator of antigen-specific CD8 T cells. In a CT26 mouse tumor model, GITRL-FP promoted expansion of antigen-specific T cells, depletion of regulatory T cells (Tregs), and generation of long-lasting CD8 T cell memory. This memory expansion was dependent on the dose of GITRL-FP and resulted in complete tumor clearance and protection from tumor rechallenge. In contrast, in TC-1 tumor-bearing mice, GITRL-FP monotherapy could not prime an antigen-specific CD8 T cell response and was unable to deplete Tregs. However, when combined with a vaccine targeting E7, treatment with GITRL-FP resulted in an augmentation of the vaccine-induced antigen-specific CD8 T cells, the depletion of Tregs, and a potent antitumor immune response. In both model systems, GITR levels on antigen-specific CD8 T cells were higher than on all other CD8 T cells, and GITRL-FP interacted directly with primed antigen-specific CD8 T cells. When taken together, our results demonstrate that the delivery of GITRL-FP as a therapeutic can promote anti-tumor responses in the presence of tumor-specific CD8 T cells. These findings support further study into combination partners for GITRL-FP that may augment CD8 T-cell priming as well as provide hypotheses that can be tested in human clinical trials exploring GITR agonists including GITRL-FP.

Twitter Demographics

The data shown below were collected from the profiles of 20 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 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 33%
Student > Ph. D. Student 10 26%
Student > Master 3 8%
Student > Bachelor 2 5%
Other 1 3%
Other 3 8%
Unknown 7 18%
Readers by discipline Count As %
Immunology and Microbiology 11 28%
Agricultural and Biological Sciences 8 21%
Biochemistry, Genetics and Molecular Biology 4 10%
Pharmacology, Toxicology and Pharmaceutical Science 3 8%
Environmental Science 1 3%
Other 1 3%
Unknown 11 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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 19 July 2017.
All research outputs
#1,746,109
of 17,904,439 outputs
Outputs from Journal for Immunotherapy of Cancer
#348
of 1,833 outputs
Outputs of similar age
#39,831
of 276,226 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#1
of 1 outputs
Altmetric has tracked 17,904,439 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,833 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.7. This one has done well, scoring higher than 81% 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 276,226 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 85% 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