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http://hdl.handle.net/2445/171366
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DC Field | Value | Language |
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dc.contributor.author | Di Mitri, Diletta | - |
dc.contributor.author | Mirenda, Michela | - |
dc.contributor.author | Vasilevska, Jelena | - |
dc.contributor.author | Calcinotto, Arianna | - |
dc.contributor.author | Delaleu, Nicolas | - |
dc.contributor.author | Revandkar, Ajinkya | - |
dc.contributor.author | Gil, Veronica | - |
dc.contributor.author | Boysen, Gunther | - |
dc.contributor.author | Losa, Marco | - |
dc.contributor.author | Mosole, Simone | - |
dc.contributor.author | Pasquini, Emiliano | - |
dc.contributor.author | Antuono, Rocco D' | - |
dc.contributor.author | Masetti, Michela | - |
dc.contributor.author | Zagato, Elena | - |
dc.contributor.author | Chiorino, Giovanna | - |
dc.contributor.author | Ostano, Paola | - |
dc.contributor.author | Rinaldi, Andrea | - |
dc.contributor.author | Gnetti, Letizia | - |
dc.contributor.author | Graupera i Garcia-Milà, Mariona | - |
dc.contributor.author | Figueiredo, Ana Raquel Martins | - |
dc.contributor.author | Pereira Mestre, Ricardo | - |
dc.contributor.author | Waugh, David | - |
dc.contributor.author | Barry, Simon | - |
dc.contributor.author | Bono, Johann Sebastian de | - |
dc.contributor.author | Alimonti, Andrea | - |
dc.date.accessioned | 2020-10-20T13:45:22Z | - |
dc.date.available | 2020-10-20T13:45:22Z | - |
dc.date.issued | 2019-08-20 | - |
dc.identifier.uri | http://hdl.handle.net/2445/171366 | - |
dc.description.abstract | Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment supporting tumorigenesis. TAMs re-education has been proposed as a strategy to promote tumor inhibition. However, whether this approach may work in prostate cancer is unknown. Here we find that Pten-null prostate tumors are strongly infiltrated by TAMs expressing C-X-C chemokine receptor type 2 (CXCR2), and activation of this receptor through CXCL2 polarizes macrophages toward an anti-inflammatory phenotype. Notably, pharmacological blockade of CXCR2 receptor by a selective antagonist promoted the re-education of TAMs toward a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in Pten(pc-/-); Trp53(pc-/-) mice differentiated in tumor necrosis factor alpha (TNF-alpha)-releasing pro-inflammatory macrophages, leading to senescence and tumor inhibition. Mechanistically, PTEN-deficient tumor cells are vulnerable to TNF-alpha-induced senescence, because of an increase of TNFR1. Our results identify TAMs as targets in prostate cancer and describe a therapeutic strategy based on CXCR2 blockade to harness anti-tumorigenic potential of macrophages against this disease. | - |
dc.format.extent | 19 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Cell Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2019.07.068 | - |
dc.relation.ispartof | Cell Reports, 2019, vol. 28, num. 8, p. 2156-2168 | - |
dc.relation.uri | https://doi.org/10.1016/j.celrep.2019.07.068 | - |
dc.rights | cc by-nc-nd (c) Di Mitri et al., 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Càncer de pròstata | - |
dc.subject.classification | Macròfags | - |
dc.subject.classification | Cèl·lules T | - |
dc.subject.other | Prostate cancer | - |
dc.subject.other | Macrophages | - |
dc.subject.other | T cells | - |
dc.title | Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-10-13T10:23:45Z | - |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/683136/EU//Immune-senescence | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 31433989 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
Files in This Item:
File | Description | Size | Format | |
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Di MitriD.pdf | 5.41 MB | Adobe PDF | View/Open |
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