Details:

Alternative Title:
J Exp Med
Publisher's site:
http://dx.doi.org/10.1084/jem.20130440
Personal Author:
Raccosta, Laura ; Fontana, Raffaella ; Maggioni, Daniela ; Lanterna, Claudia ; Villablanca, Eduardo J. ; ... More +
Raccosta, Laura ; Fontana, Raffaella ; Maggioni, Daniela ; Lanterna, Claudia ; Villablanca, Eduardo J. ; Paniccia, Aida ; Musumeci, Andrea ; Chiricozzi, Elena ; Trincavelli, Maria Letizia ; Daniele, Simona ; Martini, Claudia ; Gustafsson, Jan-Ake ; Doglioni, Claudio ; Feo, Safiyè Gonzalvo ; Leiva, Andrea ; Ciampa, Maria Grazia ; Mauri, Laura ; Sensi, Cristina ; Prinetti, Alessandro ; Eberini, Ivano ; Mora, J. Rodrigo ; Bordignon, Claudio ; Steffensen, Knut R. ; Sonnino, Sandro ; Sozzani, Silvano ; Traversari, Catia ; Russo, Vincenzo Less -
Description:
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.
Subject:
[+]
Animals
Antigens, CD11b
Antigens, Ly
Article
Cell Proliferation
Chemotaxis
Chromatography, High Pressure Liquid
Disease Models, Animal
HEK293 Cells
Humans
Hydroxycholesterols
Immunosuppression
Ligands
Mass Spectrometry
Mice
Myeloid Cells
Neoplasms
Neovascularization, Pathologic
Neutrophils
Orphan Nuclear Receptors
Receptors, G-Protein-Coupled
Receptors, Interleukin-8B
Signal Transduction
Sterols

Source:
J Exp Med. 2013; 210(9):1711-1728.
Document Type:
Journal Article
Funding:
11-0729/Association for International Cancer Research/United Kingdom ; DP2 2009A054301/DP/NCCDPHP CDC HHS/United States
11-0729/Association for International Cancer Research/United Kingdom ; DP2 2009A054301/DP/NCCDPHP CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:18665edb124553c2bfc71710cb52c7d4ddc726035cab8fe474f73b27eda6c71a
File Type:

Supporting Files

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