Traditional medicine Bazi Bushen potentiates immunosurveillance of senescent liver cancer cells via cGAS-STING signaling activation in macrophages

• Published in: Cancer letters Vol. 627; p. 217544
• Main Authors: Xing, Fuxue, Lv, Hongwei, Xiang, Wei, Wang, Liang, Zong, Qianni, Lv, Guishuai, Liu, Chunying, Feng, Qiyu, Wang, Hongyang, Yang, Wen
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.09.2025
• Subjects: Animals; Bazi Bushen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Cellular Senescence - drug effects; Cellular Senescence - immunology; cGAS-STING signaling; Humans; Immunologic Surveillance - drug effects; Immunosurveillance; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - immunology; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Macrophage; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Nucleotidyltransferases - metabolism; Senescence; Signal Transduction - drug effects; cGAS-STING signaling; Liver cancer; Immunosurveillance; Senescence; Bazi Bushen; Macrophage
• ISSN: 0304-3835; 1872-7980; 1872-7980
• DOI: 10.1016/j.canlet.2025.217544

Senescent cancer cells often evade immune clearance to exert profound effects on cancer progression and therapy resistance. Improving immunosurveillance to eliminate senescent cancer cells is a crucial measure to enhance anti-cancer therapy. Bazi Bushen (BZBS) is a traditional medicine with the function of relieving fatigue and delaying ageing, but its role in tumor treatment remains poorly understood. Herein, we find that BZBS promotes immunosurveillance of both chemotherapy- and oncogene-induced senescent liver cancer cells, further leading to enhanced chemotherapy efficacy and dramatic tumor repression in mice. Mechanistically, BZBS induces mitochondrial DNA leakage by mitochondrial damage to further activate cGAS-STING signaling in macrophages. Subsequently, cGAS-STING signaling activation in macrophages recruits CD8+ T cells into tumor and promotes the anti-tumor activity of CD8+ T cells to eradicate senescent cancer cells. Furthermore, host STING is responsible for BZBS-mediated immunosurveillance of senescent liver cancer cells in mice. Therefore, our findings unveil the role of traditional medicine BZBS in activating cGAS-STING signaling and potentiating senescence immunosurveillance to enhance anti-cancer therapy. •BZBS enhances chemotherapy efficacy and represses tumor progression in mice.•BZBS promotes immunosurveillance of senescent liver cancer cells.•BZBS induces mitochondrial DNA leakage to activate cGAS-STING signaling in macrophages.•Host STING is responsible for BZBS-mediated immunosurveillance of senescent liver cancer cells.