PMID- 30230526 OWN - NLM STAT- MEDLINE DCOM- 20190521 LR - 20231213 IS - 1097-0215 (Electronic) IS - 0020-7136 (Linking) VI - 144 IP - 7 DP - 2019 Apr 1 TI - Direct RIG-I activation in human NK cells induces TRAIL-dependent cytotoxicity toward autologous melanoma cells. PG - 1645-1656 LID - 10.1002/ijc.31874 [doi] AB - Activation of the innate immune receptor retinoic acid-inducible gene I (RIG-I) by its specific ligand 5'-triphosphate RNA (3pRNA) triggers anti-tumor immunity, which is dependent on natural killer (NK) cell activation and cytokine induction. However, to date, RIG-I expression and the functional consequences of RIG-I activation in NK cells have not been examined. Here, we show for the first time the expression of RIG-I in human NK cells and their activation upon RIG-I ligand (3pRNA) transfection. 3pRNA-activated NK cells killed melanoma cells more efficiently than NK cells activated by type I interferon. Stimulation of RIG-I in NK cells specifically increased the surface expression of membrane-bound TNF-related apoptosis-inducing ligand (TRAIL) on NK cells, while activated NK cell receptors were not affected. RIG-I-induced membrane-bound TRAIL initiated death-receptor-pathway-mediated apoptosis not only in allogeneic but also in autologous human leukocyte antigen (HLA) class I-positive and HLA class I-negative melanoma cells. These results identify the direct activation of RIG-I in NK cells as a novel mechanism for how RIG-I can trigger enhanced NK cell killing of tumor cells, underscoring the potential of RIG-I activation for tumor immunotherapy. CI - (c) 2018 UICC. FAU - Dassler-Plenker, Juliane AU - Dassler-Plenker J AUID- ORCID: 0000-0002-1782-102X AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. FAU - Paschen, Annette AU - Paschen A AD - Department of Dermatology, Venereology and Allergology, University Hospital Essen, University of Duisburg-Essen, 45112, Essen, Germany. FAU - Putschli, Bastian AU - Putschli B AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. FAU - Rattay, Stephanie AU - Rattay S AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. FAU - Schmitz, Saskia AU - Schmitz S AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. FAU - Goldeck, Marion AU - Goldeck M AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. FAU - Bartok, Eva AU - Bartok E AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. FAU - Hartmann, Gunther AU - Hartmann G AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. FAU - Coch, Christoph AU - Coch C AD - Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, University of Bonn, 53127, Bonn, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190109 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Ligands) RN - 0 (Lysosomal-Associated Membrane Protein 1) RN - 0 (Receptors, Immunologic) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFSF10 protein, human) RN - 63231-63-0 (RNA) RN - EC 3.6.1.- (RIGI protein, human) RN - EC 3.6.4.13 (DEAD Box Protein 58) SB - IM MH - Apoptosis MH - Coculture Techniques MH - Cytotoxicity, Immunologic MH - DEAD Box Protein 58/*metabolism MH - Humans MH - Killer Cells, Natural/*cytology/immunology MH - Ligands MH - Lysosomal-Associated Membrane Protein 1/metabolism MH - Melanoma/*immunology/*therapy MH - RNA/genetics/*metabolism MH - Receptors, Immunologic MH - TNF-Related Apoptosis-Inducing Ligand/*metabolism MH - Transfection MH - Transplantation, Autologous MH - Tumor Cells, Cultured OTO - NOTNLM OT - RIG-I OT - TRAIL OT - innate immunity OT - melanoma OT - natural killer (NK) cells EDAT- 2018/09/20 06:00 MHDA- 2019/05/22 06:00 CRDT- 2018/09/20 06:00 PHST- 2018/03/21 00:00 [received] PHST- 2018/07/30 00:00 [revised] PHST- 2018/08/22 00:00 [accepted] PHST- 2018/09/20 06:00 [pubmed] PHST- 2019/05/22 06:00 [medline] PHST- 2018/09/20 06:00 [entrez] AID - 10.1002/ijc.31874 [doi] PST - ppublish SO - Int J Cancer. 2019 Apr 1;144(7):1645-1656. doi: 10.1002/ijc.31874. Epub 2019 Jan 9.