Dataset related to article "Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer."
Authors/Creators
- Di Mitri D1
- Mirenda M2
- Vasilevska J2
- Calcinotto A2
- Delaleu N3
- Revandkar A2
- Gil V4,4
- Boysen G4
- Losa M2
- Mosole S2
- Pasquini E2
- D'Antuono R5,5
- Masetti M1
- Zagato E2
- Chiorino G6
- Ostano P6
- Rinaldi A2
- Gnetti L7
- Graupera M8
- Martins Figueiredo Fonseca AR8
- Pereira Mestre R9
- Waugh D10
- Barry S11
- De Bono J4
- Alimonti A12
- 1. Humanitas Clinical and Research Center – IRCCS -, via Manzoni 56, 20089 Rozzano (Mi) - Italy
- 2. Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.
- 3. Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway; Swiss Institute of Bioinformatics, Lausanne, Switzerland; 2C SysBioMed, 6646 Contra, Switzerland.
- 4. The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK.
- 5. Institute for Research in Biomedicine (IRB), 6500 Bellinzona, Switzerland.
- 6. Cancer Genomics Lab, Fondazione Edo ed Elvo Tempia, Via Malta, 3, 13900 Biella, Italy.
- 7. Pathology Unit, University Hospital of Parma, 43126 Parma, Italy.
- 8. Vascular Signalling Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain; Program Against Cancer Therapeutic Resistance (ProCURE), Barcelona, Spain; CIBERONC, Madrid, Spain.
- 9. Medical Oncology, Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland.
- 10. Movember Centre of Excellence, Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
- 11. IMED Oncology AstraZeneca, Li KaShing Centre, Cambridge, UK.
- 12. Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Faculty of Medicine, Università della Svizzera Italiana, 1011 Lugano, Switzerland; Department of Medicine, University of Padua, 35131 Padua, Italy; Medical Oncology, Oncology Institute of Southern Switzerland, 6500 Bellinzona, Switzerland
Description
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 Ptenpc-/-; Trp53pc-/- mice differentiated in tumor necrosis factor alpha (TNF-α)-releasing pro-inflammatory macrophages, leading to senescence and tumor inhibition. Mechanistically, PTEN-deficient tumor cells are vulnerable to TNF-α-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.
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Additional details
Related works
- Is supplement to
- 31433989 (PMID)
- 10.1016/j.celrep.2019.07.068 (DOI)