title: Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells.
abstract: During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression in NK cell-controlled cancers, the mechanistic cues underlying this immunosuppression remain unknown. Here, we show that IL-18 converts a subset of Kit(-) (CD11b(-)) into Kit(+) natural killer (NK) cells, which accumulate in all lymphoid organs of tumor bearers and mediate immunoablative functions. Kit(+) NK cells overexpressed B7-H1/PD-L1, a ligand for PD-1. The adoptive transfer of Kit(+) NK cells promoted tumor growth in two pulmonary metastases tumor models and significantly reduced the dendritic and NK cell pools residing in lymphoid organs in a B7-H1-dependent manner. Neutralization of IL-18 by RNA interference in tumors or systemically by IL-18-binding protein dramatically reduced the accumulation of Kit(+)CD11b(-) NK cells in tumor bearers. Together, our findings show that IL-18 produced by tumor cells elicits Kit(+)CD11b(-) NK cells endowed with B7-H1-dependent immunoablative functions in mice.
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Terme
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ullrich
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aymeric
authors.forename: Kathrin
authors.initials: K
authors.lastname: Meinhardt
authors.forename: Jérôme D
authors.initials: JD
authors.lastname: Coudert
authors.forename: Mélanie
authors.initials: M
authors.lastname: Desbois
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Sophie
authors.initials: S
authors.lastname: Viaud
authors.forename: Bernard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Salaheddine
authors.initials: S
authors.lastname: Mécheri
authors.forename: Gilles
authors.initials: G
authors.lastname: Kaplanski
authors.forename: Armelle
authors.initials: A
authors.lastname: Prévost-Blondel
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Mariapia
authors.initials: M
authors.lastname: Degli-Esposti
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000032:analysis / Q000502:physiology; D039481:CD11b Antigen / Q000032:analysis; D005260:Female; D020382:Interleukin-18 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis
chemical_list: D060890:B7-H1 Antigen; D039481:CD11b Antigen; D020382:Interleukin-18; D019009:Proto-Oncogene Proteins c-kit