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T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma

Overview of attention for article published in Clinical Cancer Research, February 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Mentioned by

news
23 news outlets
blogs
1 blog
twitter
23 tweeters
patent
1 patent
facebook
1 Facebook page

Citations

dimensions_citation
246 Dimensions

Readers on

mendeley
300 Mendeley
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Title
T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma
Published in
Clinical Cancer Research, February 2018
DOI 10.1158/1078-0432.ccr-17-1846
Pubmed ID
Authors

Karolina Woroniecka, Pakawat Chongsathidkiet, Kristen Rhodin, Hanna Kemeny, Cosette Dechant, S. Harrison Farber, Aladine A. Elsamadicy, Xiuyu Cui, Shohei Koyama, Christina Jackson, Landon J. Hansen, Tanner M. Johanns, Luis Sanchez-Perez, Vidyalakshmi Chandramohan, Yen-Rei Andrea Yu, Darell D. Bigner, Amber Giles, Patrick Healy, Glenn Dranoff, Kent J. Weinhold, Gavin P. Dunn, Peter E. Fecci

Abstract

T cell dysfunction is a hallmark of GBM. While anergy and tolerance have been well characterized, T cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amidst immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM. Tumor-infiltrating and peripheral blood lymphocytes (TIL, PBL) were isolated from patients with GBM. Levels of exhaustion-associated inhibitory receptors and post-stimulation levels of the cytokines IFN-g, TNF-a, and IL-2 were assessed by flow cytometry. T cell receptor (TCR) Vβ chain expansion was also assessed in TIL and PBL. Similar analysis was extended to TIL isolated from intracranial and subcutaneous immunocompetent murine models of glioma, breast, lung, and melanoma cancers. Our data reveal that GBM elicits a particularly severe T cell exhaustion signature among infiltrating T cells characterized by: 1) prominent upregulation of multiple immune checkpoints; 2) stereotyped T cell transcriptional programs matching classical virus-induced exhaustion; and 3) notable T cell hypo-responsiveness in tumor-specific T cells. Exhaustion signatures differ predictably with tumor identity, but remain stable across manipulated tumor locations. Distinct cancers possess similarly distinct mechanisms for exhausting T cells. The poor TIL function and severe exhaustion observed in GBM highlights the need to better understand this tumor-imposed mode of T cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM.

Twitter Demographics

The data shown below were collected from the profiles of 23 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 300 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 300 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 68 23%
Researcher 40 13%
Student > Master 28 9%
Student > Bachelor 27 9%
Student > Doctoral Student 22 7%
Other 41 14%
Unknown 74 25%
Readers by discipline Count As %
Medicine and Dentistry 56 19%
Immunology and Microbiology 54 18%
Biochemistry, Genetics and Molecular Biology 34 11%
Agricultural and Biological Sciences 24 8%
Neuroscience 15 5%
Other 24 8%
Unknown 93 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 194. 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 15 December 2021.
All research outputs
#138,067
of 20,494,250 outputs
Outputs from Clinical Cancer Research
#55
of 11,912 outputs
Outputs of similar age
#4,215
of 393,647 outputs
Outputs of similar age from Clinical Cancer Research
#2
of 164 outputs
Altmetric has tracked 20,494,250 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,912 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.0. This one has done particularly well, scoring higher than 99% 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 393,647 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 164 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.