The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
cGAS-STING–mediated DNA sensing maintains CD8 + T cell stemness and promotes antitumor T cell therapy
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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“Also, two recent reports have shown that T cell-intrinsic STING signaling could control differentiation and effector functions of CD8+ and CD4+ T cells60,61.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [61]
Citations
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Yu, L., Wei, J., & Liu, P. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.06.019 · Cited by 818
Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer
Jia, D., Wang, Q., Qi, Y., Jiang, Y., He, J., Lin, Y., Sun, Y., Xu, J., Chen, W., Fan, L., et al. (2024) · Cell · doi:10.1016/j.cell.2024.02.022 · Cited by 479
Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy
Garland, K. M., Sheehy, T. L., & Wilson, J. T. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00750 · Cited by 372
STING-induced regulatory B cells compromise NK function in cancer immunity
Li, S., Mirlekar, B., Johnson, B. M., Brickey, W. J., Wrobel, J. A., Yang, N., Song, D., Entwistle, S., Tan, X. M., Deng, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05254-3 · Cited by 359
Self-citationComprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy
Zheng, J., Mo, J., Zhu, T., Zhuo, W., Yi, Y., Hu, S., Yin, J., Zhang, W., Zhou, H., & Liu, Z. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01250-1 · Cited by 344
Metadata
- 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
- Venue
- Science Translational Medicine
- Published
- 2020-06-24
- Volume
- 12
- Issue
- 549
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- 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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