Research ArticleIMMUNOTHERAPY

NK cells mediate clearance of CD8+ T cell–resistant tumors in response to STING agonists

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Science Immunology  20 Mar 2020:
Vol. 5, Issue 45, eaaz2738
DOI: 10.1126/sciimmunol.aaz2738

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Priming NK Cells for Tumor Destruction

Tumors with low neoantigen burden and/or diminished class I MHC expression evade CD8+ T cells, but NK cells provide another option to target such tumors for immune elimination. Nicolai et al. used several mouse models to investigate the mechanisms by which intratumoral injection of a cyclic dinucleotide (CDN) agonist for STING potentiated the antitumor activity of NK cells, both in the injected tumor and at a remote, uninjected tumor site. CDN administration induced type I interferons that directly promoted NK cell activation and simultaneously enabled an indirect pathway of activation driven by induction of IL-15 and IL-15Rα on dendritic cells. These findings provide preclinical evidence that amplification of NK-based tumor immunity may offer a valuable adjunct to immunotherapy approaches promoting CD8+ T cell–dependent antitumor responses.

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