In:
Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 12, No. 549 ( 2020-06-24)
Abstract:
Although cGAS-STING–mediated DNA sensing in tumor cells or phagocytes is central for launching antitumor immunity, the role of intrinsic cGAS-STING activation in T cells remains unknown. Here, we observed that peripheral blood CD8 + T cells from patients with cancer showed remarkably compromised expression of the cGAS-STING cascade. We demonstrated that the cGAS-STING cascade in adoptively transferred CD8 + T cells was essential for antitumor immune responses in the context of T cell therapy in mice. Mechanistically, cell-autonomous cGAS and STING promoted the maintenance of stem cell–like CD8 + T cells, in part, by regulating the transcription factor TCF1 expression. Moreover, autocrine cGAS-STING–mediated type I interferon signaling augmented stem cell–like CD8 + T cell differentiation program mainly by restraining Akt activity. In addition, genomic DNA was selectively enriched in the cytosol of mouse CD8 + T cells upon in vitro and in vivo stimulation. STING agonism enhanced the formation of stem-like central memory CD8 + T cells from patients with cancer and potentiated antitumor responses of CAR-T cell therapy in a xenograft model. These findings advance our understanding of inherent cGAS-STING activation in T cells and provide insight into the development of improved T cell therapy by harnessing the cGAS-STING pathway for cancer immunotherapy.
Type of Medium:
Online Resource
ISSN:
1946-6234
,
1946-6242
DOI:
10.1126/scitranslmed.aay9013
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
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