High-Throughput Screening and Proteomic Characterization of Compounds Targeting Myeloid-Derived Suppressor Cells
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Le résumé fourni par la source
Myeloid-derived suppressor cells (MDSC) are a heterogeneous cell population of incompletely differentiated immune cells. They are known to suppress T cell activity and are implicated in multiple chronic diseases, which make them an attractive cell population for drug discovery. Here, we characterized the baseline proteomes and phospho-proteomes of mouse MDSC differentiated from a progenitor cell line to a depth of 7000 proteins and phosphorylation sites. We also validated the cellular system for drug discovery by recapitulating and identifying known and novel molecular responses to the well-studied MDSC drugs entinostat and mocetinostat. We established a high-throughput drug screening platform using a MDSC/T cell coculture system and assessed the effects of ∼21,000 small molecule compounds on T cell proliferation and IFN-γ secretion to identify novel MDSC modulator. The most promising candidates were validated in a human MDSC system, and subsequent proteomic experiments showed significant upregulation of several proteins associated with the reduction of reactive oxygen species (ROS). Proteome-wide solvent-induced protein stability assays identified Acyp1 and Cd74 as potential targets, and the ROS-reducing drug phenotype was validated by measuring ROS levels in cells in response to compound, suggesting a potential mode of action. We anticipate that the data and chemical tools developed in this study will be valuable for further research on MDSC and related drug discovery.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- High-Throughput Screening and Proteomic Characterization of Compounds Targeting Myeloid-Derived Suppressor Cells
- Date Crossref
- 01/09/2023
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Technical University of Munich Chair of Proteomics and Bioanalytics pays non établi dans la noticeUniversité ou école supérieure
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Merck KGaA pays non établi dans la noticeEntreprise
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TUM Klinikum pays non établi dans la noticeÉtablissement de santé
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Fresenius (Germany) pays non établi dans la noticeEntreprise
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Leibniz-Institute for Food Systems Biology at the Technical University of Munich pays non établi dans la noticeStructure de recherche
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Global Research & Development pays non établi dans la noticeInstitution
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OmicScouts GmbH pays non établi dans la noticeEntreprise
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TUM School of Life Sciences Chair of Molecular Nutritional Medicine pays non établi dans la noticeUniversité ou école supérieure
Chair of Proteomics and Bioanalytics — Technical University of Munich, Merck KGaA et TUM Klinikum, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.