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  3. A fluorescent STING ligand sensor for high-throughput screening of compounds that can enhance tumor immunotherapy

A fluorescent STING ligand sensor for high-throughput screening of compounds that can enhance tumor immunotherapy

  • Cell Rep Methods. 2025 Jul 21;5(7):101106. doi: 10.1016/j.crmeth.2025.101106.
Pengkai Sun 1,  Bin Wang 1,  Caiyun Liu 2,  Zixiong Wang 2,  Yang Liu 3,  Yuan-Biao Qiao 3,  Xinjian Li 4
Affiliations

Affiliations

  • 1 Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong 030619, China; State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 2 State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
  • 4 State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: lixinjian@ibp.ac.cn.
PMID: 40669456 DOI: 10.1016/j.crmeth.2025.101106
Abstract

The activation of the stimulator of interferon genes (STING) pathway triggers the release of type I interferons that can potentiate the host immune response against tumors. STING agonism is therefore a promising strategy for the development of Cancer immunotherapy; however, sensitive tools and assays for the discovery of STING modulators are currently limited. Here, we develop and characterize a STING ligand sensor, FiSL, to detect STING ligands in vitro. Utilizing FiSL, we identify honokiol, a natural compound derived from Magnolia species, as an orally available STING agonist from a bioactive compound library. Functional studies reveal that honokiol exerts antitumor activity in a STING-dependent manner. Moreover, in STING-humanized mouse tumor models, honokiol enhances the efficacy of anti-PD-(L)1 immunotherapy. Collectively, we have developed FiSL as a tool for high-throughput screening of STING ligands and revealed honokiol as a STING agonist that can be harnessed to treat human Cancer.

Keywords

CP: Cancer biology; CP: Immunology; FiSL; STING agonist; STING ligand sensor; antitumor immunity; cancer immunotherapy; honokiol.

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