强粘附性Mn2+水凝胶TACE栓塞剂对肝癌基于STING介导的免疫干预机制研究

临床仅约30%的原发性肝癌（HCC）患者适合手术治疗，但依然面临着高复发与转移风险的困扰。其中，经导管肝动脉化疗栓塞（TACE）精确阻断肝癌血供可促进肝癌细胞坏死。然而TACE术后残癌及其周围组织的缺氧会诱发缺氧诱导因子高表达，从而促进血管内皮生长因子表达增加，导致瘤体产生新的血管致使肝癌栓塞不全、残癌随血流迁移而发生复发及转移，大大降低TACE的治疗效果。本课题拟构建由Mn2+交联的复合水凝胶作为新型TACE栓塞剂用于HCC瘤体的介入治疗，通过有效改善术后的乏氧问题以避免栓塞不全，同时通过激活cGAS-STING通路以及使用PD-L1抗体激活和增强免疫治疗清除术后残癌，最终增强治疗效果。本课题试图阐明在利用TACE治疗肿瘤的同时改善乏氧环境以及通过激活机体免疫应答清除残癌对提升TACE治疗效果的重要作用。为原发性肝癌甚至其他类型癌症的治疗提供新的思路以及实验依据。

Only 30% of the patients that suffered from primary hepatocellular carcinoma (HCC) are suitable for surgical treatment in clinical. But it is still bothered with a high risk of recurrence and metastasis. Transcatheter hepatic arterial chemoembolization (TACE) can accurately block the blood supplementation of HCC and lead to cancer cell apoptosis and necrosis. However, the high expression of hypoxia-inducible factors (HIFs) that result from extreme hypoxia after TACE treatments and the residual tumors will increase the expression of vascular endothelial growth factor (VEGF), resulting in the formation of new blood vessels. Hence, the embolization effect of TACE will be compromised and the residual cancer cells will migrate to normal tissues through blood flow and lead to recurrence and metastasis, finally discounting the therapeutic effect of TACE. This study intends to construct a composite hydrogel as a new TACE embolization agent that cross-linked by Mn2+ for the interventional treatment of HCC tumors. It can effectively avoid incomplete embolism by improving the postoperative hypoxic dilemma. Meanwhile, the cGAS-STING pathway activation and PD-L1 antibody usage will ultimately enhance the therapeutic effect of TACE. This proposal attempts to demonstrate the importance of improving the hypoxic environment and removing the residual tumor by activating the immune response in achieving efficient TACE treatment. And this will provide new ideas and experimental basis for the treatment of primary liver cancer and even other types of cancer.