Journal of Clinical Hepatology
This article explores the regulatory mechanism of the cGAS-STING signaling pathway on the killing of hepatocellular carcinoma (HCC) by γδT cells through in vitro experiments. The study isolated and expanded highly pure (>99%) human peripheral blood γδT cells, treated them with agonist G10 (activating the pathway) and inhibitor H-151 (blocking the pathway) respectively, and found that the G10 group significantly upregulated the expression of STING, p-STING, TBK1, p-TBK1, IRF3, and p-IRF3 proteins, while the secretion of IFN-γ and TNF-α increased, and the killing power against MHCC-97H and Huh-7 liver cancer cells was significantly enhanced; whereas the H-151 group showed the opposite trend. The results confirm that this pathway can positively regulate the antitumor effect of γδT cells.
This study is the first to reveal in vitro that the cGAS-STING pathway is a key target for regulating the antitumor function of γδT cells, providing new strategies and theoretical basis for improving the efficacy of γδT cell adoptive immunotherapy. Its significance lies in: first, breaking through the traditional focus on TCR or co-stimulatory molecules, expanding the cognitive dimension of metabolic-immune signal cross-regulation; second, suggesting that targeting the activation of this pathway (such as combined with G10-type agonists) may enhance the response rate of clinical γδT cell treatment; third, laying a foundation for subsequent exploration of the universality of this pathway in other solid tumors (such as gastric cancer, lung cancer). Although there are limitations such as being limited to in vitro, not covering multiple factors, and not including in vivo verification, it provides an important entry point for translational medical research.
Objective: To investigate the regulatory effect of the cyclic guanosine monophosphate-adenosine monophosphate adenosine synthetase (cGA…
