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

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

doi:10.1084/jem.20130440

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

Published Date:

Jul 29 2013

Publisher's site:

http://dx.doi.org/10.1084/jem.20130440

Source:

J Exp Med. 2013; 210(9):1711-1728.

[PDF-2.58 MB]

Details:

Alternative Title:

J Exp Med

Personal Author:

Raccosta, Laura ; Fontana, Raffaella ; Maggioni, Daniela ; Lanterna, Claudia ; Villablanca, Eduardo J. ; ... More ▼

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:

[+]

Document Type:

Journal Article

Funding:

11-0729/Association for International Cancer Research/United Kingdom ; DP2 2009A054301/DP/NCCDPHP CDC HHS/United States ;

Collection(s):

CDC Public Access

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