title: 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.affiliation: Cancer Gene Therapy Unit, Program of Immunology and Bio Immuno Gene Therapy of Cancer, Division of Molecular Oncology, Scientific Institute San Raffaele, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Raccosta
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fontana
authors.forename: Daniela
authors.initials: D
authors.lastname: Maggioni
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanterna
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Villablanca
authors.forename: Aida
authors.initials: A
authors.lastname: Paniccia
authors.forename: Andrea
authors.initials: A
authors.lastname: Musumeci
authors.forename: Elena
authors.initials: E
authors.lastname: Chiricozzi
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Trincavelli
authors.forename: Simona
authors.initials: S
authors.lastname: Daniele
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Safiyè Gonzalvo
authors.initials: SG
authors.lastname: Feo
authors.forename: Andrea
authors.initials: A
authors.lastname: Leiva
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ciampa
authors.forename: Laura
authors.initials: L
authors.lastname: Mauri
authors.forename: Cristina
authors.initials: C
authors.lastname: Sensi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prinetti
authors.forename: Ivano
authors.initials: I
authors.lastname: Eberini
authors.forename: J Rodrigo
authors.initials: JR
authors.lastname: Mora
authors.forename: Claudio
authors.initials: C
authors.lastname: Bordignon
authors.forename: Knut R
authors.initials: KR
authors.lastname: Steffensen
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Catia
authors.initials: C
authors.lastname: Traversari
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D049109:Cell Proliferation; D002633:Chemotaxis; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D007165:Immunosuppression Therapy; D008024:Ligands; D000071518:Liver X Receptors; D013058:Mass Spectrometry; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D015398:Signal Transduction; D013261:Sterols / Q000378:metabolism*
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D006888:Hydroxycholesterols; D008024:Ligands; D000071518:Liver X Receptors; C480309:Ly6G antigen, mouse; D057093:Orphan Nuclear Receptors; D043562:Receptors, G-Protein-Coupled; D023063:Receptors, Interleukin-8B; D013261:Sterols; C003585:22-hydroxycholesterol
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