title: RIG-I activation induces the release of extracellular vesicles with antitumor activity.
abstract: Activation of the innate immune receptor retinoic acid-inducible gene I (RIG-I) by its specific ligand 5'-triphosphate-RNA (3pRNA) triggers antitumor immunity predominantly via NK cell activation and direct apoptosis induction in tumor cells. However, how NK cells are mobilized to attack the tumor cells remains elusive. Here, we show that RIG-I activation induced the secretion of extracellular vesicles (EVs) from melanoma cells, which by themselves revealed antitumor activityin vitroandin vivo. RIG-I-induced EVs from melanoma cells exhibited an increased expression of the NKp30-ligand (BAG6, BAT3) on their surface triggering NK cell-mediated lysis of melanoma cells via activation of the cytotoxicity NK cell-receptor NKp30. Moreover, systemic administration of RIG-I-induced melanoma-EVs showed a potent antitumor activity in a melanoma mouse modelin vivo. In conclusion, our data establish a new RIG-I-dependent pathway leading to NK cell-mediated tumor cell killing.
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn , Bonn, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Daßler-Plenker
authors.affiliation: Clinic I for Internal Medicine, Innate immunity Group, University of Cologne , Cologne, Germany.
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Reiners
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn , Bonn, Germany.
authors.forename: Jasper G
authors.initials: JG
authors.lastname: van den Boorn
authors.affiliation: Clinic I for Internal Medicine, Innate immunity Group, University of Cologne , Cologne, Germany.
authors.forename: Hinrich P
authors.initials: HP
authors.lastname: Hansen
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn , Bonn, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Putschli
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, Albert-Ludwigs-University , Freiburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Barnert
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn , Bonn, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Schuberth-Wagner
authors.affiliation: Department of Pharmaceutical Technology and Biopharmacy, Albert-Ludwigs-University , Freiburg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Schubert
authors.affiliation: Department of Dermatology and Allergy, University of Bonn , Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tüting
authors.affiliation: Clinic I for Internal Medicine, Innate immunity Group, University of Cologne , Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallek
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn , Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlee
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn , Bonn, Germany.
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.affiliation: Clinic I for Internal Medicine, Innate immunity Group, University of Cologne, Cologne, Germany; Experimental Tumor Research, Center for Tumor Biology and Immunology, Clinic for Hematology, Oncology, and Immunology, Philipps University, Hans-Meerwein-Strasse 3, Marburg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Pogge von Strandmann
authors.affiliation: Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn , Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Coch
keywords: BAG6; NK cells; NKp30; RIG-I; exosomes; extracellular vesicles; melanoma