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T cells in multiple myeloma display features of exhaustion and senescence at the tumor site

Overview of attention for article published in Journal of Hematology & Oncology, November 2016
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

Mentioned by

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6 tweeters
wikipedia
5 Wikipedia pages

Citations

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138 Dimensions

Readers on

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132 Mendeley
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Title
T cells in multiple myeloma display features of exhaustion and senescence at the tumor site
Published in
Journal of Hematology & Oncology, November 2016
DOI 10.1186/s13045-016-0345-3
Pubmed ID
Authors

Claudia Zelle-Rieser, Shanmugapriya Thangavadivel, Rainer Biedermann, Andrea Brunner, Patrizia Stoitzner, Ella Willenbacher, Richard Greil, Karin Jöhrer

Abstract

Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments. In addition, T cell function concerning proliferation and expression of T-bet, IL-2, IFNγ, and CD107a was investigated after in vitro stimulation by CD3/CD28. Finally, data was compared to healthy, age-matched donor T cells from both compartments. Multicolor flow cytometry was utilized for the analyses of surface molecules, intracellular staining of cytokines was also performed by flow cytometry, and proliferation was assessed by (3)H-thymidine incorporation. Statistical analyses were performed utilizing unpaired T test and Mann-Whitney U test. We observed enhanced T cell exhaustion and senescence especially at the tumor site. CD8+ T cells expressed several molecules associated with T cell exhaustion (PD-1, CTLA-4, 2B4, CD160) and T cell senescence (CD57, lack of CD28). This phenotype was associated with lower proliferative capacity and impaired function. Despite a high expression of the transcription factor T-bet, CD8+ T cells from the tumor site failed to produce IFNγ after CD3/CD28 in vitro restimulation and displayed a reduced ability to degranulate in response to T cell stimuli. Notably, the percentage of senescent CD57+CD28- CD8+ T cells was significantly lower in treated myeloma patients when compared to untreated patients. T cells from the bone marrow of myeloma patients were more severely impaired than peripheral T cells. While our data suggest that terminally differentiated cells are preferentially deleted by therapy, immune-checkpoint molecules were still present on T cells supporting the potential of checkpoint inhibitors to reactivate T cells in myeloma patients in combination therapies. However, additional avenues to restore anti-myeloma T cell responses are urgently needed.

Twitter Demographics

The data shown below were collected from the profiles of 6 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 132 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 132 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 24 18%
Student > Master 18 14%
Student > Ph. D. Student 17 13%
Student > Bachelor 12 9%
Student > Doctoral Student 11 8%
Other 23 17%
Unknown 27 20%
Readers by discipline Count As %
Immunology and Microbiology 26 20%
Biochemistry, Genetics and Molecular Biology 24 18%
Medicine and Dentistry 17 13%
Agricultural and Biological Sciences 15 11%
Unspecified 4 3%
Other 16 12%
Unknown 30 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 23 August 2021.
All research outputs
#4,245,770
of 21,181,573 outputs
Outputs from Journal of Hematology & Oncology
#273
of 1,077 outputs
Outputs of similar age
#80,454
of 314,804 outputs
Outputs of similar age from Journal of Hematology & Oncology
#16
of 91 outputs
Altmetric has tracked 21,181,573 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,077 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.8. This one has gotten more attention than average, scoring higher than 74% 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 314,804 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 91 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.