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http://hdl.handle.net/2445/171366
Title: | Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer |
Author: | Di Mitri, Diletta Mirenda, Michela Vasilevska, Jelena Calcinotto, Arianna Delaleu, Nicolas Revandkar, Ajinkya Gil, Veronica Boysen, Gunther Losa, Marco Mosole, Simone Pasquini, Emiliano Antuono, Rocco D' Masetti, Michela Zagato, Elena Chiorino, Giovanna Ostano, Paola Rinaldi, Andrea Gnetti, Letizia Graupera i Garcia-Milà, Mariona Figueiredo, Ana Raquel Martins Pereira Mestre, Ricardo Waugh, David Barry, Simon Bono, Johann Sebastian de Alimonti, Andrea |
Keywords: | Càncer de pròstata Macròfags Cèl·lules T Prostate cancer Macrophages T cells |
Issue Date: | 20-Aug-2019 |
Publisher: | Cell Press |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2019.07.068 |
It is part of: | Cell Reports, 2019, vol. 28, num. 8, p. 2156-2168 |
URI: | http://hdl.handle.net/2445/171366 |
Related resource: | https://doi.org/10.1016/j.celrep.2019.07.068 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
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