The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils
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 antitu...
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| Veröffentlicht in: | The Journal of experimental medicine 2013-08, Vol.210 (9), p.1711-1728 |
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| creator | 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. |
| doi_str_mv | 10.1084/jem.20130440 |
| format | Article |
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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.</description><identifier>ISSN: 0022-1007</identifier><identifier>ISSN: 1540-9538</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20130440</identifier><identifier>PMID: 23897983</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Animals ; Antigens, Ly - metabolism ; CD11b Antigen - metabolism ; Cell Proliferation ; Chemotaxis ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; HEK293 Cells ; Humans ; Hydroxycholesterols - metabolism ; Immunosuppression Therapy ; Ligands ; Liver X Receptors ; Mass Spectrometry ; Mice ; Myeloid Cells - metabolism ; Myeloid Cells - pathology ; Neoplasms - blood supply ; Neoplasms - metabolism ; Neoplasms - pathology ; Neovascularization, Pathologic - metabolism ; Neovascularization, Pathologic - pathology ; Neutrophils - metabolism ; Orphan Nuclear Receptors - metabolism ; Receptors, G-Protein-Coupled - metabolism ; Receptors, Interleukin-8B - metabolism ; Signal Transduction ; Sterols - metabolism</subject><ispartof>The Journal of experimental medicine, 2013-08, Vol.210 (9), p.1711-1728</ispartof><rights>2013 Raccosta et al. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-8795777675264d6851905bdf183ba5a9147e3ce4bbfaa51626bcd97193fbe6453</citedby><cites>FETCH-LOGICAL-c521t-8795777675264d6851905bdf183ba5a9147e3ce4bbfaa51626bcd97193fbe6453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,550,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23897983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:127285627$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Raccosta, Laura</creatorcontrib><creatorcontrib>Fontana, Raffaella</creatorcontrib><creatorcontrib>Maggioni, Daniela</creatorcontrib><creatorcontrib>Lanterna, Claudia</creatorcontrib><creatorcontrib>Villablanca, Eduardo J</creatorcontrib><creatorcontrib>Paniccia, Aida</creatorcontrib><creatorcontrib>Musumeci, Andrea</creatorcontrib><creatorcontrib>Chiricozzi, Elena</creatorcontrib><creatorcontrib>Trincavelli, Maria Letizia</creatorcontrib><creatorcontrib>Daniele, Simona</creatorcontrib><creatorcontrib>Martini, Claudia</creatorcontrib><creatorcontrib>Gustafsson, Jan-Ake</creatorcontrib><creatorcontrib>Doglioni, Claudio</creatorcontrib><creatorcontrib>Feo, Safiyè Gonzalvo</creatorcontrib><creatorcontrib>Leiva, Andrea</creatorcontrib><creatorcontrib>Ciampa, Maria Grazia</creatorcontrib><creatorcontrib>Mauri, Laura</creatorcontrib><creatorcontrib>Sensi, Cristina</creatorcontrib><creatorcontrib>Prinetti, Alessandro</creatorcontrib><creatorcontrib>Eberini, Ivano</creatorcontrib><creatorcontrib>Mora, J Rodrigo</creatorcontrib><creatorcontrib>Bordignon, Claudio</creatorcontrib><creatorcontrib>Steffensen, Knut R</creatorcontrib><creatorcontrib>Sonnino, Sandro</creatorcontrib><creatorcontrib>Sozzani, Silvano</creatorcontrib><creatorcontrib>Traversari, Catia</creatorcontrib><creatorcontrib>Russo, Vincenzo</creatorcontrib><title>The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><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.</description><subject>Animals</subject><subject>Antigens, Ly - metabolism</subject><subject>CD11b Antigen - metabolism</subject><subject>Cell Proliferation</subject><subject>Chemotaxis</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Disease Models, Animal</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Hydroxycholesterols - metabolism</subject><subject>Immunosuppression Therapy</subject><subject>Ligands</subject><subject>Liver X Receptors</subject><subject>Mass Spectrometry</subject><subject>Mice</subject><subject>Myeloid Cells - metabolism</subject><subject>Myeloid Cells - pathology</subject><subject>Neoplasms - blood supply</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Neovascularization, Pathologic - metabolism</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Neutrophils - metabolism</subject><subject>Orphan Nuclear Receptors - metabolism</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Receptors, Interleukin-8B - metabolism</subject><subject>Signal Transduction</subject><subject>Sterols - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqFkc9LHDEYhoO06Lr15rnk2EPH5uckuRTK0qogFIqFQg8hM_uNG52ZTJOMdf97U3YVPfWUkPfJy_fxIHRKyRklWny6heGMEcqJEOQALagUpDKS6zdoQQhjFSVEHaHjlG4JoULI-hAdMa6NMpov0O_rDeDwsE0ZYuir1a_VD4bdg0946t02YYfvYItLBNiPOBc4QhtnnwcYMw4dzvMQYjXFMITsxxs8wpxjmDa-T-_Q2871CU725xL9_Pb1enVRXX0_v1x9uapayWiutDJSKVUryWqxrrWkhshm3VHNGyedoUIBb0E0TeecpDWrm3ZtFDW8a6AWki9RtetNf2GaGztFP7i4tcF5u3-6KzewkimtReE_7_iSDLBuyybR9a--vU5Gv7E34d5yJYVWrBR82BfE8GeGlO3gUwt970YIc7JUljEF07X4P1owSYUpApfo4w5tY0gpQvc8ESX2n2pbVNsn1QV__3KLZ_jJLX8E7lml2Q</recordid><startdate>20130826</startdate><enddate>20130826</enddate><creator>Raccosta, Laura</creator><creator>Fontana, Raffaella</creator><creator>Maggioni, Daniela</creator><creator>Lanterna, Claudia</creator><creator>Villablanca, Eduardo J</creator><creator>Paniccia, Aida</creator><creator>Musumeci, Andrea</creator><creator>Chiricozzi, Elena</creator><creator>Trincavelli, Maria Letizia</creator><creator>Daniele, Simona</creator><creator>Martini, Claudia</creator><creator>Gustafsson, Jan-Ake</creator><creator>Doglioni, Claudio</creator><creator>Feo, Safiyè Gonzalvo</creator><creator>Leiva, Andrea</creator><creator>Ciampa, Maria Grazia</creator><creator>Mauri, Laura</creator><creator>Sensi, Cristina</creator><creator>Prinetti, Alessandro</creator><creator>Eberini, Ivano</creator><creator>Mora, J Rodrigo</creator><creator>Bordignon, Claudio</creator><creator>Steffensen, Knut R</creator><creator>Sonnino, Sandro</creator><creator>Sozzani, Silvano</creator><creator>Traversari, Catia</creator><creator>Russo, Vincenzo</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20130826</creationdate><title>The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils</title><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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-8795777675264d6851905bdf183ba5a9147e3ce4bbfaa51626bcd97193fbe6453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antigens, Ly - 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| subjects | Animals Antigens, Ly - metabolism CD11b Antigen - metabolism Cell Proliferation Chemotaxis Chromatography, High Pressure Liquid Disease Models, Animal HEK293 Cells Humans Hydroxycholesterols - metabolism Immunosuppression Therapy Ligands Liver X Receptors Mass Spectrometry Mice Myeloid Cells - metabolism Myeloid Cells - pathology Neoplasms - blood supply Neoplasms - metabolism Neoplasms - pathology Neovascularization, Pathologic - metabolism Neovascularization, Pathologic - pathology Neutrophils - metabolism Orphan Nuclear Receptors - metabolism Receptors, G-Protein-Coupled - metabolism Receptors, Interleukin-8B - metabolism Signal Transduction Sterols - metabolism |
| title | The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils |
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