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Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models

Overview of attention for article published in Cancer Immunology, Immunotherapy, June 2018
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3 tweeters

Citations

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12 Dimensions

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24 Mendeley
Title
Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models
Published in
Cancer Immunology, Immunotherapy, June 2018
DOI 10.1007/s00262-018-2186-0
Pubmed ID
Authors

Robert D. Leone, Im-Meng Sun, Min-Hee Oh, Im-Hong Sun, Jiayu Wen, Judson Englert, Jonathan D. Powell

Abstract

Adenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy. Herein, we demonstrate the ability of the novel A2aR antagonist, CPI-444, to dramatically enhance immunologic responses in models of checkpoint therapy and ACT in cancer. Furthermore, we demonstrate that A2aR blockade with CPI-444 decreases expression of multiple checkpoint pathways, including PD-1 and LAG-3, on both CD8+ effector T cells (Teff) and FoxP3+ CD4+ regulatory T cells (Tregs). Interestingly, our studies demonstrate that A2aR blockade likely has its most profound effects during Teff cell activation, significantly decreasing PD-1 and LAG-3 expression at the draining lymph nodes of tumor bearing mice. In contrast to previous reports using A2aR knockout models, pharmacologic blockade with CPI-444 did not impede CD8 T cell persistence or memory recall. Overall these findings not only redefine our understanding of the mechanisms by which adenosine inhibits immunity but also have important implications for the design of novel immunotherapy regimens.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 24 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 6 25%
Researcher 5 21%
Student > Ph. D. Student 4 17%
Student > Bachelor 4 17%
Other 2 8%
Other 3 13%
Readers by discipline Count As %
Unspecified 6 25%
Biochemistry, Genetics and Molecular Biology 5 21%
Immunology and Microbiology 4 17%
Pharmacology, Toxicology and Pharmaceutical Science 3 13%
Agricultural and Biological Sciences 3 13%
Other 3 13%

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 29 June 2018.
All research outputs
#8,250,878
of 13,157,264 outputs
Outputs from Cancer Immunology, Immunotherapy
#1,446
of 1,872 outputs
Outputs of similar age
#160,726
of 268,286 outputs
Outputs of similar age from Cancer Immunology, Immunotherapy
#13
of 28 outputs
Altmetric has tracked 13,157,264 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,872 research outputs from this source. They receive a mean Attention Score of 4.5. This one is in the 16th percentile – i.e., 16% 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 268,286 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 28 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.