Carvedilol sensitizes chemotherapy by targeting STING to boost anti-tumor immunity

  • Cell Rep. 2025 May 27;44(5):115572. doi: 10.1016/j.celrep.2025.115572.
Yifang Dang  1 ,  Mingtong Ma  2 ,  Yan Wang  3 ,  Mengmeng Zhao  4 ,  Yajuan Cao  5 ,  Hang Su  6 ,  Tianhao Liu  3 ,  Mengge Zheng  3 ,  Jiani Gao  6 ,  Xiangyang Wu  7 ,  Junfang Xu  8 ,  Li Chen  7 ,  Jianzhong Jeff Xi  9 ,  Yiyan Fei  10 ,  Haipeng Liu  11
Affiliations
  • 1. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Department of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai 200072, China; Central Laboratory, Taicang Hospital Affiliated to Soochow University, Taicang 215400, China.
  • 2. Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 3. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Department of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai 200072, China.
  • 4. Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 5. Department of Integrated Traditional Chinese and Western Medicine, Tongji University School of Medicine, Shanghai 200433, China.
  • 6. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 7. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 8. Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
  • 9. State Key Laboratory of Natural and Biomimetic Drugs, Institute of Molecular Medicine, Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
  • 10. Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai 200433, China.
  • 11. Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Department of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: [email protected].
PMID: 40249703 DOI: 10.1016/j.celrep.2025.115572
Abstract

The stimulator of interferon genes (STING)-mediated type I interferon (IFN) response is critical for mounting anti-tumor immunity and sensitizing chemotherapy by remodeling the tumor immune microenvironment. However, no clinically available drugs have been applied for STING activation. Based on high-throughput screening of small-molecule microarrays, we found that carvedilol, an Adrenergic Receptor blocker used to treat essential hypertension and symptomatic heart failure, is a STING Activator. Mechanistically, carvedilol interacts with STING at threonine 263 and enhances its dimerization. Importantly, carvedilol enhances the therapeutic effect of etoposide in both the allografted tumor model and patient-derived tumor-like cell clusters (PTCs) by promoting etoposide-induced STING activation. Our findings identify carvedilol as a STING Activator and provide a theoretical basis for combining carvedilol and etoposide in Cancer therapy.

Keywords
CP: Cancer; CP: Immunology; STING; carvedilol; combination therapy; etoposide; type I IFN response.
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