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Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma

Overview of attention for article published in Journal for Immunotherapy of Cancer, May 2016
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Title
Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma
Published in
Journal for Immunotherapy of Cancer, May 2016
DOI 10.1186/s40425-016-0132-2
Pubmed ID
Authors

Mira A. Patel, Jennifer E. Kim, Debebe Theodros, Ada Tam, Esteban Velarde, Christina M. Kochel, Brian Francica, Thomas R. Nirschl, Ali Ghasemzadeh, Dimitrios Mathios, Sarah Harris-Bookman, Christopher C. Jackson, Christina Jackson, Xiaobu Ye, Phuoc T. Tran, Betty Tyler, Vladimir Coric, Mark Selby, Henry Brem, Charles G. Drake, Drew M. Pardoll, Michael Lim

Abstract

Glioblastoma (GBM) is a poorly immunogenic neoplasm treated with focused radiation. Immunotherapy has demonstrated synergistic survival effects with stereotactic radiosurgery (SRS) in murine GBM. GITR is a co-stimulatory molecule expressed constitutively on regulatory T-cells and by effector T-cells upon activation. We tested the hypothesis that anti-GITR monoclonal antibody (mAb) and SRS together would confer an immune-mediated survival benefit in glioma using the orthotopic GL261 glioma model. Mice received SRS and anti-GITR 10 days after implantation. The anti-GITR mAbs tested were formatted as mouse IgG1 D265A (anti-GITR (1)) and IgG2a (anti-GITR (2a)) isotypes. Mice were randomized to four treatment groups: (1) control; (2) SRS; (3) anti-GITR; (4) anti-GITR/SRS. SRS was delivered to the tumor in one fraction, and mice were treated with mAb thrice. Mice were euthanized on day 21 to analyze the immunologic profile of tumor, spleen, and tumor draining lymph nodes. Anti-GITR (1)/SRS significantly improved survival over either treatment alone (p < .0001) with a cure rate of 24 % versus 0 % in a T-lymphocyte-dependent manner. There was elevated intratumoral CD4+ effector cell infiltration relative to Treg infiltration in mice treated with anti-GITR (1)/SRS, as well as significantly elevated IFNγ and IL-2 production by CD4+ T-cells and elevated IFNγ and TNFα production by CD8+ T-cells. There was increased mRNA expression of M1 markers and decreased expression of M2 markers in tumor infiltrating mononuclear cells. The anti-GITR (2a)/SRS combination did not improve survival, induce tumor regression, or result in Treg depletion. These findings provide preclinical evidence for the use of anti-GITR (1) non-depleting antibodies in combination with SRS in GBM.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Unknown 74 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 17 23%
Student > Ph. D. Student 16 21%
Student > Doctoral Student 7 9%
Student > Bachelor 7 9%
Other 6 8%
Other 8 11%
Unknown 14 19%
Readers by discipline Count As %
Medicine and Dentistry 20 27%
Immunology and Microbiology 10 13%
Agricultural and Biological Sciences 9 12%
Engineering 5 7%
Biochemistry, Genetics and Molecular Biology 3 4%
Other 10 13%
Unknown 18 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 04 September 2017.
All research outputs
#17,285,036
of 25,371,288 outputs
Outputs from Journal for Immunotherapy of Cancer
#2,887
of 3,421 outputs
Outputs of similar age
#216,114
of 342,340 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#12
of 15 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,421 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.4. This one is in the 11th percentile – i.e., 11% 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 342,340 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.