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

Details

• Alternative Title:
  J Exp Med
• Personal Author:
  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
• 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.
• Subjects:
  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

  More +
• 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
• Volume:
  210
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:18665edb124553c2bfc71710cb52c7d4ddc726035cab8fe474f73b27eda6c71a
• Download URL:
  https://stacks.cdc.gov/view/cdc/22507/cdc_22507_DS1.pdf
• File Type:
  [PDF - 2.58 MB ]