NK cells mediate clearance of CD8 <sup>+</sup> T cell–resistant tumors in response to STING agonists
Christopher J. Nicolai, Natalie K. Wolf, I-Chang Chang, Georgia Kirn, Assaf Marcus, Chudi Ndubaku, Sarah M. McWhirter, David H. Raulet
Abstract
T cells. CDNs enhanced NK cell activation, cytotoxicity, and antitumor effects in part by inducing type I interferon (IFN). IFN acted in part directly on NK cells in vivo and in part indirectly via the induction of IL-15 and IL-15 receptors, which were important for CDN-induced NK activation and tumor control. After in vivo administration of CDNs, dendritic cells (DCs) up-regulated IL-15Rα in an IFN-dependent manner. Mice lacking the type I IFN receptor specifically on DCs had reduced NK cell activation and tumor control. Therapeutics that activate NK cells, such as CDNs, checkpoint inhibitors, NK cell engagers, and cytokines, may represent next-generation approaches to cancer immunotherapy.