| First Author | Di Mitri D | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 8 | Pages | 2156-2168.e5 |
| PubMed ID | 31433989 | Mgi Jnum | J:285688 |
| Mgi Id | MGI:6400160 | Doi | 10.1016/j.celrep.2019.07.068 |
| Citation | Di Mitri D, et al. (2019) Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer. Cell Rep 28(8):2156-2168.e5 |
| abstractText | 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. |
