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

被引：181

作者：

Raccosta, Laura ^{[1
]}

Fontana, Raffaella ^{[1
]}

Maggioni, Daniela ^{[1
]}

Lanterna, Claudia ^{[1
]}

Villablanca, Eduardo J. ^{[3
]}

Paniccia, Aida ^{[1
]}

Musumeci, Andrea ^{[1
]}

Chiricozzi, Elena ^{[4
]}

Trincavelli, Maria Letizia ^{[5
]}

Daniele, Simona ^{[5
]}

Martini, Claudia ^{[5
]}

Gustafsson, Jan-Ake ^{[6
,7
]}

Doglioni, Claudio ^{[2
,8
]}

Feo, Safiye Gonzalvo ^{[9
]}

Leiva, Andrea ^{[1
]}

Ciampa, Maria Grazia ^{[4
]}

Mauri, Laura ^{[4
]}

Sensi, Cristina ^{[10
]}

Prinetti, Alessandro ^{[4
]}

Eberini, Ivano ^{[10
]}

Mora, J. Rodrigo ^{[3
]}

Bordignon, Claudio ^{[8
,11
]}

Steffensen, Knut R. ^{[6
]}

Sonnino, Sandro ^{[4
]}

Sozzani, Silvano ^{[9
,12
]}

Traversari, Catia ^{[11
]}

Russo, Vincenzo ^{[1
]}

机构：

[1] Ist Sci San Raffaele, Canc Gene Therapy Unit, Program Immunol & Bio Immuno Gene Therapy Canc, Div Mol Oncol, I-20132 Milan, Italy

[2] Ist Sci San Raffaele, Dept Pathol, I-20132 Milan, Italy

[3] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[4] Univ Milan, Dept Med Chem Biochem & Biotechnol, Ctr Excellence Neurodegenerat Dis, I-20090 Segrate, Italy

[5] Univ Pisa, Dept Pharm, I-56126 Pisa, Italy

[6] Karolinska Inst, Dept Biosci & Nutr, S-14183 Huddinge, Sweden

[7] Univ Houston, Ctr Nucl Receptors & Cell Signaling, Houston, TX 77204 USA

[8] Univ Vita Salute San Raffaele, I-20132 Milan, Italy

[9] Humanitas Clin & Res Ctr, I-20089 Rozzano, Italy

[10] Univ Milan, Prote & Prot Struct Study Grp, Dept Pharmacol Sci, I-20133 Milan, Italy

[11] MolMed SpA, I-20132 Milan, Italy

[12] Univ Brescia, Dept Mol & Translat Med, I-25123 Brescia, Italy

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2013年 / 210卷 / 09期

关键词：

MYELOID CELLS; DENDRITIC CELLS; CANCER; CHOLESTEROL; ANGIOGENESIS; MIGRATION; IDENTIFICATION; INFLAMMATION; METABOLISM; EXPRESSION;

D O I：

10.1084/jem.20130440

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1711 / 1728

页数：18

共 60 条

[1] A CXCL1 Paracrine Network Links Cancer Chemoresistance and Metastasis [J].