Pu Shuangpeng, Liu Tianguang, Gao Yuan, Wu Zhenyu, Liu Sulai
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Department of Anatomy and K. K. Leung Brain Research Centre, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Int Immunopharmacol. 2025 Jun 12;161:115013. doi: 10.1016/j.intimp.2025.115013.
Recent studies have revealed that the malignant progression of hepatocellular carcinoma (HCC) not only stems from tumor cell-intrinsic genetic alterations but is dynamically regulated by the tumor microenvironment (TME). As a pivotal component of TME, tumor-associated endothelial cells (TECs) critically drive HCC progression through dual mechanisms of vascular abnormality and immune modulation. TECs establish a pro-tumorigenic niche by constructing disordered vascular networks while concurrently secreting immunosuppressive factors that induce immune cell dysfunction. This review systematically examines the molecular mechanisms underlying the dynamic transition from hepatic endothelial cells to TECs, identifies key TEC subtypes mediating tumor angiogenesis and immune evasion, and elucidates their crosstalk with immunosuppressive components. Additionally, we highlight TEC-specific biomarkers associated with clinical HCC progression and synthesize current clinical trials targeting TEC-mediated pathways. These findings provide novel insights for developing precision therapies that disrupt the TEC-TME-immune axis in HCC.
最近的研究表明，肝细胞癌（HCC）的恶性进展不仅源于肿瘤细胞内在的基因改变，还受到肿瘤微环境（TME）的动态调节。作为TME的关键组成部分，肿瘤相关内皮细胞（TECs）通过血管异常和免疫调节的双重机制严重推动HCC进展。TECs通过构建无序的血管网络，同时分泌诱导免疫细胞功能障碍的免疫抑制因子，建立促肿瘤微环境。本综述系统地研究了肝内皮细胞向TECs动态转变的分子机制，确定了介导肿瘤血管生成和免疫逃逸的关键TEC亚型，并阐明了它们与免疫抑制成分的相互作用。此外，我们强调了与临床HCC进展相关的TEC特异性生物标志物，并综合了目前针对TEC介导途径的临床试验。这些发现为开发破坏HCC中TEC-TME-免疫轴的精准疗法提供了新的见解。
