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2019-08-20

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cc by-nc-nd (c) Di Mitri et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171366

Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer

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Recurs relacionat

https://doi.org/10.1016/j.celrep.2019.07.068

Resum

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.

Matèries

Càncer de pròstata, Macròfags, Cèl·lules T

Matèries (anglès)

Prostate cancer, Macrophages, T cells

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
<b>Publicacions de projectes de recerca finançats per la UE</b>

Citació

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. Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer. _Cell Reports_. 2019. Vol. 28, núm. 8, pàgs. 2156-2168. [consulta: 21 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/171366]

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