Research ArticleCancer

cGAS-STING–mediated DNA sensing maintains CD8+ T cell stemness and promotes antitumor T cell therapy

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Science Translational Medicine  24 Jun 2020:
Vol. 12, Issue 549, eaay9013
DOI: 10.1126/scitranslmed.aay9013

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Intuitive CD8+ T cells sense DNA

Stimulator of interferon genes (STING) agonism is an area of active exploration for cancer immunotherapy. Li et al. examined the cGAS-STING DNA sensing cascade in antitumor CD8+ T cells. They observed dampened STING activity in CD8+ T cells from patients with cancer or mice implanted with tumors. STING signaling supported a stem-like memory phenotype in the T cells, which is known to be beneficial for responses to immunotherapy. Cytosolic DNA was enriched in activated T cells, and STING agonism improved efficacy of adoptive cell therapy in multiple mouse models. These results highlight that CD8+ T cell DNA sensing could be exploited for therapeutic benefit in immunotherapy.

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