| Autor: |
Lu, Lu, Yang, Chao, Zhou, Xingyue, Wu, Lingling, Hong, Xiaochuan, Li, Wenwen, Wang, Xinran, Yang, Yuanqin, Cao, Dongqing, Zhang, Ao, Di, Wen, Deng, Liufu |
| Zdroj: |
Cell Reports; 20230101, Issue: Preprints |
| Abstrakt: |
Natural killer (NK) cells are cytotoxic innate lymphocytes that eradicate tumor cells. Inducing durable antitumor immune responses by NK cells represents a major priority of cancer immunotherapy. While cytosolic DNA sensing plays an essential role in initiating antitumor immunity, the role of NK cell-intrinsic STING signaling remains unclear. Here, we find that NK cell-intrinsic STING promotes antitumor responses and maintains a reservoir of TCF-1+NK cells. In contrast, tumor cell-intrinsic cGAS and mtDNA are required for NK cell antitumor activity, indicating that tumor mtDNA recognition by cGAS partially triggers NK cell-intrinsic STING activation. Moreover, addition of cGAMP enables STING activation and type I interferon production in NK cells, thereby supporting the activation of NK cells in vitro. In humans, STING agonism promotes the expansion of TCF-1+NK cells. This study provides insight into understanding how STING signaling drives NK cell antitumor immunity and the development of NK cell-based cancer immunotherapy. |
| Databáze: |
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