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
The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils / L. Raccosta, R. Fontana, D. Maggioni, C. Lanterna, E.J. Villablanca, A. Paniccia, A. Musumeci, E. Chiricozzi, M.L. Trincavelli, S. Daniele, C. Martini, J. Gustafsson, C. Doglioni, S.G. Feo, A. Leiva, M.G. Ciampa, L. Mauri, C. Sensi, A. Prinetti, I. Eberini, J.R. Mora, C. Bordignon, K.R. Steffensen, S. Sonnino, S. Sozzani, C. Traversari, V. Russo. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 210:9(2013 Aug 26), pp. 1711-1728.
The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils
E. Chiricozzi;M.G. Ciampa;L. Mauri;C. Sensi;A. Prinetti;I. Eberini;S. Sonnino;
2013
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
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
