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American Association for Cancer Research

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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
  • Among the highest-scoring outputs from this source (#50 of 11,789)
  • 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
213 Dimensions

Readers on

mendeley
278 Mendeley
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 278 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 278 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 66 24%
Researcher 37 13%
Student > Master 24 9%
Student > Bachelor 24 9%
Student > Doctoral Student 22 8%
Other 34 12%
Unknown 71 26%
Readers by discipline Count As %
Medicine and Dentistry 53 19%
Immunology and Microbiology 49 18%
Biochemistry, Genetics and Molecular Biology 29 10%
Agricultural and Biological Sciences 23 8%
Neuroscience 14 5%
Other 20 7%
Unknown 90 32%

Attention Score in Context

This research output has an Altmetric Attention Score of 195. 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
#131,941
of 20,009,828 outputs
Outputs from Clinical Cancer Research
#50
of 11,789 outputs
Outputs of similar age
#4,155
of 390,652 outputs
Outputs of similar age from Clinical Cancer Research
#2
of 164 outputs
Altmetric has tracked 20,009,828 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 11,789 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.8. 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 390,652 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.