肠道菌群在肝细胞癌免疫抑制微环境中的作用机制与治疗策略

Mechanisms and therapeutic strategies of gut microbiota in the immune‑suppressive micro-environment of hepatocellular carcinoma

  • 摘要: 肝细胞癌为全世界癌症相关死亡的第3大病因,其晚期患者的治疗选择有限且预后欠佳。肝细胞癌的肿瘤微环境具有显著的免疫抑制特征,主要表现为髓源性抑制细胞扩增、调节性T细胞浸润增多以及肿瘤相关巨噬细胞向M2型极化,这些改变共同推动了免疫逃逸现象的发生,并降低了免疫治疗的效能。近年来的研究表明:肠道菌群失调借助肠‑肝轴在塑造肝细胞癌免疫抑制微环境过程中发挥着重要作用,且基于肠道菌群失调的相关干预策略展现出了潜在的治疗价值。然而,肠道菌群调控肝细胞癌免疫抑制微环境形成的分子机制存在异质性,临床转化亦面临诸多难题。笔者全面梳理肠道菌群失调调控肝细胞癌免疫抑制微环境的机制及最新进展,并对相关治疗策略的应用研究进行总结及展望,旨在为肝细胞癌的免疫治疗提供全新的理论依据与潜在靶点。

     

    Abstract: Hepatocellular carcinoma (HCC), the third leading cause of cancer‑related death worldwide, has limited treatment options and poor prognosis for advanced patients. The tumor microenvironment of HCC is characterized by significant immune‑suppressive features, primarily manifested through the expansion of myeloid‑derived suppressor cells, increased infiltration of regulatory T cells, and polarization of tumor‑associated macrophages towards the M2 phenotype. These alterations collectively promote immune evasion and diminish the efficacy of immuno-therapies. Recent studies have revealed that gut microbiota dysbiosis plays a crucial role in shaping the immune‑suppressive microenvironment of HCC via the gut‑liver axis. Furthermore, intervention strategies targeting gut microbiota dysbiosis have demonstrated potential therapeutic value. However, the molecular mechanisms by which the gut microbiota regulates the formation of HCC immune-suppressive microenvironment are heterogeneous, and clinical translation faces numerous challenges that require further investigation. The authors review comprehensively the mechanisms by which gut microbiota dysbiosis regulates the immune‑suppressive tumor microenvironment in HCC, sum-marize the latest advances in related therapeutic strategies, and provide an outlook on their clinical application. The aim is to offer new theoretical foundations and potential therapeutic targets for HCC immunotherapy.

     

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