Wnt/β-catenin inhibitor ICG-001 enhances the antitumor efficacy of radiotherapy by increasing radiation-induced DNA damage and improving tumor immune microenvironment in hepatocellular carcinoma

Highlights: • ICG-001 increases intrinsic radiosensitivity and activates radiation-regulated TIME of HCC. • ICG-001 improves radiation-regulated TIME by enhancing cGAS/STING pathway activation. • ICG-001 increases RT effects in tumor control, survival prolong, and recurrence prevention. • ICG-001 might be a synergetic treatment for radioimmunotherapy in HCC patients. Radiotherapy (RT) has a promising anti-tumor effect depending on its effects on both cancer cells and tumor immune microenvironment (TIME). As one of the most common alterations in hepatocellular carcinoma (HCC), wnt/β-catenin pathway activation, has been reported to induce radioresistance and suppressive TIME. In this study, we aim to explore the effect of wnt/β-catenin inhibitor ICG-001 on radiosensitivity and RT-related TIME of HCC and the underlying mechanism.