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Direct RIG-I activation in human NK cells induces TRAIL-dependent cytotoxicity toward autologous melanoma cells.
- Source :
-
International journal of cancer [Int J Cancer] 2019 Apr 01; Vol. 144 (7), pp. 1645-1656. Date of Electronic Publication: 2019 Jan 09. - Publication Year :
- 2019
-
Abstract
- 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.<br /> (© 2018 UICC.)
- Subjects :
- Apoptosis
Coculture Techniques
Cytotoxicity, Immunologic
Humans
Killer Cells, Natural immunology
Ligands
Lysosomal-Associated Membrane Protein 1 metabolism
RNA genetics
Receptors, Immunologic
Transfection
Transplantation, Autologous
Tumor Cells, Cultured
DEAD Box Protein 58 metabolism
Killer Cells, Natural cytology
Melanoma immunology
Melanoma therapy
RNA metabolism
TNF-Related Apoptosis-Inducing Ligand metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 144
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 30230526
- Full Text :
- https://doi.org/10.1002/ijc.31874