TY - JOUR
T1 - The soluble α chain of interleukin-15 receptor
T2 - A proinflammatory molecule associated with tumor progression in head and neck cancer
AU - Badoual, Cécile
AU - Bouchaud, Grégory
AU - Agueznay, Nour El Houda
AU - Mortier, Erwan
AU - Hans, Stéphane
AU - Gey, Alain
AU - Fernani, Fahima
AU - Peyrard, Séverine
AU - Laurent-Puig, Pierre
AU - Bruneval, Patrick
AU - Sastre, Xavier
AU - Plet, Ariane
AU - Garrigue-Antar, Laure
AU - Quintin-Colonna, Françoise
AU - Fridman, Wolf H.
AU - Brasnu, Daniel
AU - Jacques, Yannick
AU - Tartour, Eric
PY - 2008/5/15
Y1 - 2008/5/15
N2 - Interleukin (IL)-15 is a proinflammatory cytokine, as it induces the production of inflammatory cytokines [IL-6, tumor necrosis factor α (TNFα), IL-17, etc.]. A correlation between high intratumoral IL-15 concentrations and poor clinical outcome in lung and head and neck cancer patients has been recently reported. The purpose of this study was to investigate the role of the soluble A chain of IL-15 receptor (sIL-15Rα), a natural regulator of IL-15, in head and neck cancer. Fifty-three newly diagnosed untreated head and neck cancer patients were included in this study. Quantification of sIL-15Rα was performed with a newly developed RIA. Increased serum sIL-15Rα concentrations were found in head and neck cancer patients and were closely correlated with poor clinical outcome both in terms of locoregional control and survival even on multivariate analysis. sIL-15Rα was mainly produced by tumor cells via proteolytic cleavage of IL-15Rα mediated by ADAM-17. A correlation was observed between ADAM-17 expression in tumor cells and serum sIL-15Rα concentrations. Surprisingly, sIL-15Rα did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15-induced proinflammatory cytokines (IL-6, TNFα, and IL-17) that may promote tumor progression. This new tumor evasion mechanism based on amplification of the intratumoral inflammatory reaction is probably not restricted to head and neck cancer, as other tumors have been shown to release sIL-15Rα. Overall, these results support for the first time an original protumor role of sIL-15Rα in cancer.
AB - Interleukin (IL)-15 is a proinflammatory cytokine, as it induces the production of inflammatory cytokines [IL-6, tumor necrosis factor α (TNFα), IL-17, etc.]. A correlation between high intratumoral IL-15 concentrations and poor clinical outcome in lung and head and neck cancer patients has been recently reported. The purpose of this study was to investigate the role of the soluble A chain of IL-15 receptor (sIL-15Rα), a natural regulator of IL-15, in head and neck cancer. Fifty-three newly diagnosed untreated head and neck cancer patients were included in this study. Quantification of sIL-15Rα was performed with a newly developed RIA. Increased serum sIL-15Rα concentrations were found in head and neck cancer patients and were closely correlated with poor clinical outcome both in terms of locoregional control and survival even on multivariate analysis. sIL-15Rα was mainly produced by tumor cells via proteolytic cleavage of IL-15Rα mediated by ADAM-17. A correlation was observed between ADAM-17 expression in tumor cells and serum sIL-15Rα concentrations. Surprisingly, sIL-15Rα did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15-induced proinflammatory cytokines (IL-6, TNFα, and IL-17) that may promote tumor progression. This new tumor evasion mechanism based on amplification of the intratumoral inflammatory reaction is probably not restricted to head and neck cancer, as other tumors have been shown to release sIL-15Rα. Overall, these results support for the first time an original protumor role of sIL-15Rα in cancer.
UR - http://www.scopus.com/inward/record.url?scp=45549100198&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-6842
DO - 10.1158/0008-5472.CAN-07-6842
M3 - Article
C2 - 18483276
AN - SCOPUS:45549100198
SN - 0008-5472
VL - 68
SP - 3907
EP - 3914
JO - Cancer Research
JF - Cancer Research
IS - 10
ER -