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The RNA-binding Protein MEX3B Mediates Resistance to Cancer Immunotherapy by Downregulating HLA-A Expression

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

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • Good Attention Score compared to outputs of the same age and source (77th percentile)

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11 X users
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2 patents
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1 Google+ user

Citations

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77 Dimensions

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80 Mendeley
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Title
The RNA-binding Protein MEX3B Mediates Resistance to Cancer Immunotherapy by Downregulating HLA-A Expression
Published in
Clinical Cancer Research, July 2018
DOI 10.1158/1078-0432.ccr-17-2483
Pubmed ID
Authors

Lu Huang, Shruti Malu, Jodi A. McKenzie, Miles C. Andrews, Amjad H. Talukder, Trang Tieu, Tatiana Karpinets, Cara Haymaker, Marie-Andrée Forget, Leila J. Williams, Zhe Wang, Rina M. Mbofung, Zhi-Qiang Wang, Richard Eric Davis, Roger S. Lo, Jennifer A. Wargo, Michael A. Davies, Chantale Bernatchez, Timothy Heffernan, Rodabe N. Amaria, Anil Korkut, Weiyi Peng, Jason Roszik, Gregory Lizée, Scott E. Woodman, Patrick Hwu

Abstract

Cancer immunotherapy has shown promising clinical outcomes in many patients. However, some patients still fail to respond, and new strategies are needed to overcome resistance. The purpose of this study was to identify novel genes and understand the mechanisms that confer resistance to cancer immunotherapy. To identify genes mediating resistance to T cell killing, we performed an open reading frame (ORF) screen of a kinome library to study whether overexpression of a gene in patient-derived melanoma cells could inhibit their susceptibility to killing by autologous Tumor-Infiltrating Lymphocytes (TILs). The RNA-binding protein MEX3B was identified as a top candidate that decreased the susceptibility of melanoma cells to killing by TILs. Further analyses of anti-PD-1-treated melanoma patient tumor samples suggested that higherMEX3Bexpression is associated with resistance to PD-1 blockade. In addition, significantly decreased levels of IFNγ were secreted from TILs incubated with MEX3B-overexpressing tumor cells. Interestingly, this phenotype was rescued upon overexpression of exogenous HLA-A2. Consistent with this, we observed decreased HLA-A expression in MEX3B-overexpressing tumor cells. Finally, luciferase reporter assays and RNA-binding protein immunoprecipitation assays suggest that this is due to MEX3B binding to the 3' UTR ofHLA-Ato destabilize the mRNA. MEX3B mediates resistance to cancer immunotherapy by binding to the 3' UTR ofHLA-Ato destabilize theHLA-AmRNA and thus downregulate HLA-A expression on the surface of tumor cells, thereby making the tumor cells unable to be recognized and killed by T cells.

X Demographics

X Demographics

The data shown below were collected from the profiles of 11 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 80 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 80 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 18%
Researcher 12 15%
Student > Bachelor 9 11%
Other 7 9%
Student > Master 6 8%
Other 11 14%
Unknown 21 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 21 26%
Medicine and Dentistry 15 19%
Immunology and Microbiology 7 9%
Agricultural and Biological Sciences 6 8%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 9 11%
Unknown 20 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 27 December 2022.
All research outputs
#2,838,172
of 24,220,739 outputs
Outputs from Clinical Cancer Research
#2,487
of 12,951 outputs
Outputs of similar age
#56,367
of 331,025 outputs
Outputs of similar age from Clinical Cancer Research
#39
of 167 outputs
Altmetric has tracked 24,220,739 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,951 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 11.4. This one has done well, scoring higher than 80% 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 331,025 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 167 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.