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http://hdl.handle.net/2445/173234
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DC Field | Value | Language |
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dc.contributor.author | Verdura, Sara | - |
dc.contributor.author | Cuyàs, Elisabet | - |
dc.contributor.author | Cortada, Eric | - |
dc.contributor.author | Brunet, Joan | - |
dc.contributor.author | López Bonet, Eugeni | - |
dc.contributor.author | Martin Castillo, Begoña | - |
dc.contributor.author | Bosch Barrera, Joaquim | - |
dc.contributor.author | Encinar, José Antonio | - |
dc.contributor.author | Menendez, Javier A. | - |
dc.date.accessioned | 2021-01-20T07:13:42Z | - |
dc.date.available | 2021-01-20T07:13:42Z | - |
dc.date.issued | 2020-01-15 | - |
dc.identifier.uri | http://hdl.handle.net/2445/173234 | - |
dc.description.abstract | New strategies to block the immune evasion activity of programmed death ligand-1 (PD-L1) are urgently needed. When exploring the PD-L1-targeted effects of mechanistically diverse metabolism-targeting drugs, exposure to the dietary polyphenol resveratrol (RSV) revealed its differential capacity to generate a distinct PD-L1 electrophoretic migration pattern. Using biochemical assays, computer-aided docking/molecular dynamics simulations, and fluorescence microscopy, we found that RSV can operate as a direct inhibitor of glyco-PD-L1-processing enzymes (alpha-glucosidase/alpha-mannosidase) that modulate N-linked glycan decoration of PD-L1, thereby promoting the endoplasmic reticulum retention of a mannose-rich, abnormally glycosylated form of PD-L1. RSV was also predicted to interact with the inner surface of PD-L1 involved in the interaction with PD-1, almost perfectly occupying the target space of the small compound BMS-202 that binds to and induces dimerization of PD-L1. The ability of RSV to directly target PD-L1 interferes with its stability and trafficking, ultimately impeding its targeting to the cancer cell plasma membrane. Impedance-based real-time cell analysis (xCELLigence) showed that cytotoxic T-lymphocyte activity was notably exacerbated when cancer cells were previously exposed to RSV. This unforeseen immunomodulating mechanism of RSV might illuminate new approaches to restore T-cell function by targeting the PD-1/PD-L1 immunologic checkpoint with natural polyphenols. | - |
dc.format.extent | 27 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Impact Journals Llc | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.18632/aging.102646 | - |
dc.relation.ispartof | Aging-us, 2020, vol. 12, num. 1, p. 8-34 | - |
dc.relation.uri | https://doi.org/10.18632/aging.102646 | - |
dc.rights | cc by (c) Verdura et al. 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Immunoteràpia | - |
dc.subject.classification | Cèl·lules T | - |
dc.subject.classification | Fenols | - |
dc.subject.other | Immunotherapy | - |
dc.subject.other | T cells | - |
dc.subject.other | Phenols | - |
dc.title | Resveratrol targets PD-L1 glycosylation and dimerization to enhance antitumor T-cell immunity | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-12-21T13:17:14Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31901900 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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VerduraS.pdf | 4.83 MB | Adobe PDF | View/Open |
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