The oxysterol-cxcr2 axis plays a key role in the recruitment of tumor-promoting neutrophils

Laura Raccosta, Raffaella Fontana, Daniela Maggioni, Claudia Lanterna, Eduardo J. Villablanca, Aida Paniccia, Andrea Musumeci, Elena Chiricozzi, Maria Letizia Trincavelli, Simona Daniele, Claudia Martini, Jan Ake Gustafsson, Claudio Doglioni, Safiyè Gonzalvo Feo, Andrea Leiva, Maria Grazia Ciampa, Laura Mauri, Cristina Sensi, Alessandro Prinetti, Ivano EberiniJ. Rodrigo Mora, Bordignon Claudio Bordignon, Knut R. Steffensen, Sandro Sonnino, Silvano Sozzani, Catia Traversari, Vincenzo Russo

Research output: Contribution to journalArticle

102 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)1711-1728
Number of pages18
JournalJournal of Experimental Medicine
Volume210
Issue number9
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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