Cited by 305interferon and immune responsesImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers

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

Li, Wenwen, Lu, Lu, Lu, Juanjuan, Wang, Xinran, Yang, Chao, Jin, Jingsi, Wu, Lingling, Hong, Xiaochuan, Li, Fanlin, Cao, Dongqing, Yang, Yuanqin, Wu, Meng, Su, Bing, Cheng, Jinke, Yang, Xuanming, Di, Wen, Deng, Liufu·2020·Science Translational Medicine

DOI 10.1126/scitranslmed.aay9013

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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.

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Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy
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Authors: Li, W., Lu, L., Lu, J., Wang, X., Yang, C., Jin, J., Wu, L., Hong, X., Li, F., Cao, D., Yang, Y., Wu, M., Su, B., Cheng, J., Yang, X., Di, W., & Deng, L.
Affiliations: Shanghai Jiao Tong University (CN)
Corresponding author: Li, Wenwen
Lu, Lu
Yang, Xuanming
Di, Wen
Deng, Liufu
ORCID: Li, Wenwen
Lu, Lu
Lu, Juanjuan
Wang, Xinran
Yang, Chao
Jin, Jingsi
Wu, Lingling
Hong, Xiaochuan
Li, Fanlin
Cao, Dongqing
Yang, Yuanqin
Wu, Meng
Su, Bing
Cheng, Jinke
Yang, Xuanming
Di, Wen
Deng, Liufu
Venue: Science Translational Medicine
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2020-06-24
Volume: 12
Issue: 549
ISSN: 1946-6234 (ISSN-L)
1946-6242
DOI: 10.1126/scitranslmed.aay9013
OpenAlex: W3038007966
Cited by: 305
References: 54
Citations by year: 2026: 62 · 2025: 75 · 2024: 56 · 2023: 45 · 2022: 39 · 2021: 21 · 2020: 7
FWCI: 9.79
Type: journal article
Language: en
Open access: closed
Locations: Science Translational Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81771682, 81702804, 31900649)
Science and Technology Commission of Shanghai Municipality (16JC1406000)
Shanghai Municipal Commission of Health and Family Planning
Shanghai Municipal Health Commission (20194Y0625)
Innovative research team of high-level local universities in Shanghai
National Thousand Youth Talents Program
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: cGAS-STING pathway, DNA sensing, CD8+ T cells, T cell stemness, antitumor immunity, CAR T-cell therapy, cancer immunotherapy
MeSH terms: Animals, DNA, Humans, Membrane Proteins, Nucleotidyltransferases, CD8-Positive T-Lymphocytes, Mice, Cell- and Tissue-Based Therapy

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

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