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Rockefeller University Press, Journal of Experimental Medicine, 9(210), p. 1711-1728, 2013

DOI: 10.1084/jem.20130440

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

Journal article published in 2013 by Laura Raccosta ORCID, Raffaella Fontana, Daniela Maggioni, Claudia Lanterna, Eduardo J. Villablanca ORCID, Aida Paniccia, Andrea Musumeci, Elena Chiricozzi, Maria Letizia Trincavelli ORCID, Simona Daniele, Claudia Martini ORCID, Jan-Ake Gustafsson, Claudio Doglioni, Safiyè Gonzalvo Feo, Andrea Leiva and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.