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

Abstract

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.