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Direct RIG‐I activation in human NK cells induces TRAIL‐dependent cytotoxicity toward autologous melanoma cells
Author(s) -
DaßlerPlenker Juliane,
Paschen Annette,
Putschli Bastian,
Rattay Stephanie,
Schmitz Saskia,
Goldeck Marion,
Bartok Eva,
Hartmann Gunther,
Coch Christoph
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31874
Subject(s) - lymphokine activated killer cell , biology , interleukin 21 , cd49b , janus kinase 3 , innate immune system , rig i , microbiology and biotechnology , nk 92 , interleukin 12 , cancer research , immunotherapy , immunology , immune system , cytotoxic t cell , t cell , in vitro , biochemistry
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.