RIG-I activation induces the release of extracellular vesicles with antitumor activity.
RIG-I activation induces the release of extracellular vesicles with antitumor activity.
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DOI：
10.1080/2162402x.2016.1219827
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发表时间：
2016
期刊：
影响因子：
7.2
通讯作者：
Coch C
中科院分区：
文献类型：
--
作者：
Daßler-Plenker J;Reiners KS;van den Boorn JG;Hansen HP;Putschli B;Barnert S;Schuberth-Wagner C;Schubert R;Tüting T;Hallek M;Schlee M;Hartmann G;Pogge von Strandmann E;Coch C
天然免疫受体维甲酸诱导基因I(RIG-I)被其特异性配体5‘-三磷酸-RNA(3pRNA)激活，主要通过NK细胞激活和直接诱导肿瘤细胞凋亡来触发抗肿瘤免疫。然而，NK细胞如何被动员起来攻击肿瘤细胞仍然是个谜。在这里，我们展示了RIG-I激活诱导黑色素瘤细胞分泌细胞外小泡(EVS)，这本身就显示了体外和体内的抗肿瘤活性。RIG-I诱导的黑色素瘤细胞EV表面NKp30配体(BAG6，BAT3)表达增加，通过激活细胞毒NK细胞受体NKp30，触发NK细胞介导的黑色素瘤细胞裂解。此外，RIG-I诱导的黑色素瘤EVS系统给药在体内黑色素瘤小鼠模型中显示出强大的抗肿瘤活性。总之，我们的数据建立了一条新的依赖Rig I的途径，导致NK细胞介导的肿瘤细胞杀伤。
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 activity in vitro and in 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 model in vivo. In conclusion, our data establish a new RIG-I-dependent pathway leading to NK cell-mediated tumor cell killing.