1. The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils
- Author
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Claudia Lanterna, Vincenzo Russo, Eduardo J. Villablanca, Ivano Eberini, Alessandro Prinetti, Silvano Sozzani, Laura Raccosta, Elena Chiricozzi, Claudia Martini, Maria Letizia Trincavelli, Cristina Sensi, Andrea Musumeci, Safiyè Gonzalvo Feo, Andrea Leiva, Claudio Doglioni, Daniela Maggioni, Sandro Sonnino, Laura Mauri, Jan-Åke Gustafsson, Catia Traversari, Simona Daniele, Aida Paniccia, Raffaella Fontana, J. Rodrigo Mora, Knut R. Steffensen, Maria Grazia Ciampa, Claudio Bordignon, Raccosta, L, Fontana, R, Maggioni, D, Lanterna, C, Villablanca, Ej, Paniccia, A, Musumeci, A, Chiricozzi, E, Trincavelli, Ml, Daniele, S, Martini, C, Gustafsson, Ja, Doglioni, Claudio, Feo, Sg, Leiva, A, Ciampa, Mg, Mauri, L, Sensi, C, Prinetti, A, Eberini, I, Mora, Jr, Bordignon, Claudio, Steffensen, Kr, Sonnino, S, Sozzani, S, Traversari, C, and Russo, V.
- Subjects
Oxysterol ,Neutrophils ,Immunology ,Biology ,Ligands ,Mass Spectrometry ,Receptors, Interleukin-8B ,Article ,Receptors, G-Protein-Coupled ,Mice ,Immune system ,Neoplasms ,polycyclic compounds ,Immunology and Allergy ,Animals ,Antigens, Ly ,Humans ,Myeloid Cells ,CXC chemokine receptors ,Dendritic cell migration ,Liver X receptor ,Chromatography, High Pressure Liquid ,Cell Proliferation ,Liver X Receptors ,Immunosuppression Therapy ,CD11b Antigen ,Neovascularization, Pathologic ,Cell growth ,Chemotaxis ,Orphan Nuclear Receptors ,Hydroxycholesterols ,Cell biology ,Disease Models, Animal ,Sterols ,HEK293 Cells ,lipids (amino acids, peptides, and proteins) ,Signal transduction ,Signal Transduction - Abstract
Tumor-derived oxysterols recruit protumor neutrophils in an LXR-independent, CXCR2-dependent manner, thus favoring tumor growth by promoting neoangiogenesis and immunosuppression., 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.
- Published
- 2013