title: The soluble alpha chain of interleukin-15 receptor: a proinflammatory molecule associated with tumor progression in head and neck cancer.
abstract: Interleukin (IL)-15 is a proinflammatory cytokine, as it induces the production of inflammatory cytokines [IL-6, tumor necrosis factor alpha (TNFalpha), 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 alpha chain of IL-15 receptor (sIL-15Ralpha), 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-15Ralpha was performed with a newly developed RIA. Increased serum sIL-15Ralpha 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-15Ralpha was mainly produced by tumor cells via proteolytic cleavage of IL-15Ralpha mediated by ADAM-17. A correlation was observed between ADAM-17 expression in tumor cells and serum sIL-15Ralpha concentrations. Surprisingly, sIL-15Ralpha did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15-induced proinflammatory cytokines (IL-6, TNFalpha, 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-15Ralpha. Overall, these results support for the first time an original protumor role of sIL-15Ralpha in cancer.
authors.affiliation: EA 4054 Université Paris Descartes, Faculté de Medecine; Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Badoual
authors.forename: Grégory
authors.initials: G
authors.lastname: Bouchaud
authors.forename: Nour El Houda
authors.initials: Nel H
authors.lastname: Agueznay
authors.forename: Erwan
authors.initials: E
authors.lastname: Mortier
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hans
authors.forename: Alain
authors.initials: A
authors.lastname: Gey
authors.forename: Fahima
authors.initials: F
authors.lastname: Fernani
authors.forename: Séverine
authors.initials: S
authors.lastname: Peyrard
authors.forename: Pierre Laurent
authors.initials: PL
authors.lastname: -Puig
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre
authors.forename: Ariane
authors.initials: A
authors.lastname: Plet
authors.forename: Laure
authors.initials: L
authors.lastname: Garrigue-Antar
authors.forename: Françoise
authors.initials: F
authors.lastname: Quintin-Colonna
authors.forename: Wolf H
authors.initials: WH
authors.lastname: Fridman
authors.forename: Daniel
authors.initials: D
authors.lastname: Brasnu
authors.forename: Yannick
authors.initials: Y
authors.lastname: Jacques
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis; D000072198:ADAM17 Protein; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D007249:Inflammation; D019409:Interleukin-15 / Q000378:metabolism; D053720:Interleukin-15 Receptor alpha Subunit / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D008954:Models, Biological; D015999:Multivariate Analysis; D011379:Prognosis; D020033:Protein Isoforms; D011863:Radioimmunoassay
chemical_list: D003432:Cross-Linking Reagents; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D020033:Protein Isoforms; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human