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miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction

Overview of attention for article published in Journal of Translational Medicine, April 2016
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  • Above-average Attention Score compared to outputs of the same age (53rd percentile)
  • Good Attention Score compared to outputs of the same age and source (66th percentile)

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Title
miR-29b and miR-198 overexpression in CD8+ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction
Published in
Journal of Translational Medicine, April 2016
DOI 10.1186/s12967-016-0841-9
Pubmed ID
Authors

Margherita Gigante, Paola Pontrelli, Wolfgang Herr, Maddalena Gigante, Morena D’Avenia, Gianluigi Zaza, Elisabetta Cavalcanti, Matteo Accetturo, Giuseppe Lucarelli, Giuseppe Carrieri, Michele Battaglia, Walter J. Storkus, Loreto Gesualdo, Elena Ranieri

Abstract

Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells. We investigated gene expression profiles of tumor-reactive CD8(+) T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8(+) T cells from 25 RCC patients compared to 15 healthy volunteers. We observed that CD8(+) T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation-associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8(+) T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8(+) T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro. Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8(+) T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo.

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X Demographics

The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 16%
Student > Bachelor 7 16%
Researcher 7 16%
Student > Master 5 12%
Student > Doctoral Student 2 5%
Other 4 9%
Unknown 11 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 13 30%
Medicine and Dentistry 5 12%
Agricultural and Biological Sciences 2 5%
Psychology 2 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 5%
Other 8 19%
Unknown 11 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 13 April 2016.
All research outputs
#12,951,914
of 22,860,626 outputs
Outputs from Journal of Translational Medicine
#1,476
of 4,001 outputs
Outputs of similar age
#138,343
of 300,920 outputs
Outputs of similar age from Journal of Translational Medicine
#26
of 83 outputs
Altmetric has tracked 22,860,626 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,001 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.5. This one has gotten more attention than average, scoring higher than 62% 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 300,920 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 53% of its contemporaries.
We're also able to compare this research output to 83 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.