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Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma

Overview of attention for article published in Clinical Epigenetics, June 2018
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Title
Assessment of new HDAC inhibitors for immunotherapy of malignant pleural mesothelioma
Published in
Clinical Epigenetics, June 2018
DOI 10.1186/s13148-018-0517-9
Pubmed ID
Authors

Douae Bensaid, Thibaut Blondy, Sophie Deshayes, Virginie Dehame, Philippe Bertrand, Marc Grégoire, Mohammed Errami, Christophe Blanquart

Abstract

Malignant pleural mesothelioma (MPM) is a very rare and highly aggressive cancer of the pleura associated in most cases with asbestos exposure. To date, no really efficient treatments are available for this pathology. Recently, it has been shown that epigenetic drugs, particularly DNA methylation or histone acetylation modulating agents, could be very efficient in terms of cytotoxicity for several types of cancer cells. We previously showed that a hypomethylating agent (decitabine) and a histone deacetylase inhibitor (HDACi) (valproic acid (VPA)) combination was immunogenic and led to the induction of an anti-tumor immune response in a mice model of mesothelioma. However, VPA is not very specific, is active at millimolar concentrations and is responsible for side effects in clinic. To improve this approach, we studied four newly synthetized HDACi, two hydroxamates (ODH and NODH) and two benzamides (ODB and NODB), in comparison with VPA and SAHA. We evaluated their toxicity on immune cells and their immunogenicity on MPM cells in combination with decitabine. All the tested HDACi were toxic for immune cells at high concentrations. Combination with decitabine increased toxicity of HDACi only towards T-cell clone. A decrease in the proportion of regulatory T cells and natural killer cells was observed in particular with VPA and ODH. In MPM cells, all HDACi combinations induced NY-ESO-1 cancer testis antigen (CTA) expression and the recognition of the treated cells by a NY-ESO-1 specific T-CD8 clone. However, for MAGE-A1, MAGE-A3 and XAGE-1b mRNA expression, the results obtained depended on the HDACi used and on the CTA studied. Depending on the MPM cell line studied, molecules alone increased moderately PD-L1 expression. When combined, a higher stimulation of this immune check point inhibitor expression was observed. Decitabine-induced anti-viral response seemed to be inhibited in the presence of HDACi. This work shows that the combination of decitabine and HDACi could be of interest for MPM immunotherapy. However, this combination induced PD-L1 expression which suggests that an association with anti-PD-L1 therapy should be performed to induce an efficient anti-tumor immune response.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 15%
Researcher 6 13%
Student > Ph. D. Student 6 13%
Student > Doctoral Student 5 10%
Other 3 6%
Other 7 15%
Unknown 14 29%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 21%
Medicine and Dentistry 9 19%
Chemistry 3 6%
Agricultural and Biological Sciences 3 6%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Other 4 8%
Unknown 17 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 28 June 2018.
All research outputs
#15,010,626
of 23,090,520 outputs
Outputs from Clinical Epigenetics
#796
of 1,270 outputs
Outputs of similar age
#197,264
of 328,114 outputs
Outputs of similar age from Clinical Epigenetics
#22
of 29 outputs
Altmetric has tracked 23,090,520 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,270 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
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 328,114 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.