The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils.

Abstract

Tumor-infiltrating immune cells can be conditioned by molecules released within the microenvironment to thwart antitumor immune responses, thereby facilitating tumor growth. Among immune cells, neutrophils play an important protumorigenic role by favoring neoangiogenesis and/or by suppressing antitumor immune responses. Tumor-derived oxysterols have recently been shown to favor tumor growth by inhibiting dendritic cell migration toward lymphoid organs. We report that tumor-derived oxysterols recruit protumor neutrophils in a liver X receptor (LXR)-independent, CXCR2-dependent manner, thus favoring tumor growth by promoting neoangiogenesis and immunosuppression. We demonstrate that interfering with the oxysterol-CXCR2 axis delays tumor growth and prolongs the overall survival of tumor-bearing mice. These results identify an unanticipated protumor function of the oxysterol-CXCR2 axis and a possible target for cancer therapy.

• Authors: Laura Raccosta, Raffaella Fontana, Daniela Maggioni, Claudia Lanterna, Eduardo J Villablanca, Aida Paniccia, Andrea Musumeci, Elena Chiricozzi, Maria Letizia Trincavelli, Simona Daniele, Claudia Martini, Jan-Ake Gustafsson, Claudio Doglioni, Safiyè Gonzalvo Feo, Andrea Leiva, Maria Grazia Ciampa, Laura Mauri, Cristina Sensi, Alessandro Prinetti, Ivano Eberini, J Rodrigo Mora, Claudio Bordignon, Knut R Steffensen, Sandro Sonnino, Silvano Sozzani, Catia Traversari, Vincenzo Russo
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 210 Issue 9 Pg. 1711-28 (Aug 26 2013) ISSN: 1540-9538 [Electronic] United States
• PMID: 23897983 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Ly
• CD11b Antigen
• Hydroxycholesterols
• Ligands
• Liver X Receptors
• Ly6G antigen, mouse
• Orphan Nuclear Receptors
• Receptors, G-Protein-Coupled
• Receptors, Interleukin-8B
• Sterols
• 22-hydroxycholesterol

Topics

• Animals
• Antigens, Ly (metabolism)
• CD11b Antigen (metabolism)
• Cell Proliferation
• Chemotaxis
• Chromatography, High Pressure Liquid
• Disease Models, Animal
• HEK293 Cells
• Humans
• Hydroxycholesterols (metabolism)
• Immunosuppression Therapy
• Ligands
• Liver X Receptors
• Mass Spectrometry
• Mice
• Myeloid Cells (metabolism, pathology)
• Neoplasms (blood supply, metabolism, pathology)
• Neovascularization, Pathologic (metabolism, pathology)
• Neutrophils (metabolism)
• Orphan Nuclear Receptors (metabolism)
• Receptors, G-Protein-Coupled (metabolism)
• Receptors, Interleukin-8B (metabolism)
• Signal Transduction
• Sterols (metabolism)