Feng Tang, Yang Xinrui, Wang Qiwei, Liu Xiaoheng
（ 610041） Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Jan 20;55(1):6-12. doi: 10.12182/20240160203.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Due to the insidious onset and rapid progression and a lack of effective treatments, the prognosis of patients with HCC is extremely poor, with the average 5-year survival rate being less than 10%. The tumor microenvironment (TME), the internal environment in which HCC develops, can regulate the oncogenesis, development, invasion, and metastasis of HCC. During the process of cancer progression, HCC cells can regulate the biological behaviors of tumor cells, cancer-associated fibroblasts, cancer-associated immune cells, and other cells in the TME by releasing exosomes containing specific signals, thereby promoting cancer progression. However, the exact molecular mechanisms and the roles of exosomes in the specific cellular regulation of these processes are not fully understood. Herein, we summarized the TME components of HCC, the sources and the biological traits of exosomes in the TME, and the impact of mechanical factors on exosomes. In addition, special attention was given to the discussion of the effects of HCC-exosomes on different types of cells in the microenvironment. There are still many difficulties to be overcome before exosomes can be applied as carriers in clinical cancer treatment. First of all, the homogeneity of exosomes is difficult to ensure. Secondly, exosomes are mainly administered through subcutaneous injection. Although this method is simple and easy to implement, the absorption efficiency is not ideal. Thirdly, exosome extraction methods are limited in number and inefficient, making it difficult to prepare exosomes in large quantities. It is important to ensure that exosomes are used in sufficient quantities to trigger an effective tumor immune response, especially for exosome-mediated tumor immunotherapy. With the improvement in identification, isolation, and purification technology, exosomes are expected to be successfully used in the clinical diagnosis of early-stage HCC and the clinical treatment of liver cancer.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。由于其起病隐匿、进展迅速且缺乏有效的治疗方法，HCC患者的预后极差，平均5年生存率不到10%。肿瘤微环境（TME）是HCC发生发展的内部环境，可调节HCC的肿瘤发生、发展、侵袭和转移。在癌症进展过程中，HCC细胞可通过释放含有特定信号的外泌体来调节TME中肿瘤细胞、癌症相关成纤维细胞、癌症相关免疫细胞等细胞的生物学行为，从而促进癌症进展。然而，外泌体在这些过程的特定细胞调节中的具体分子机制和作用尚未完全明确。在此，我们总结了HCC的TME成分、TME中外泌体的来源和生物学特性，以及机械因素对外泌体的影响。此外，还特别讨论了HCC外泌体对微环境中不同类型细胞的作用。在外泌体能够作为载体应用于临床癌症治疗之前，仍有许多困难需要克服。首先，外泌体的同质性难以保证。其次，外泌体主要通过皮下注射给药。虽然这种方法简单易行，但吸收效率并不理想。第三，外泌体提取方法数量有限且效率低下，难以大量制备外泌体。确保使用足够数量的外泌体以引发有效的肿瘤免疫反应非常重要，特别是对于外泌体介导的肿瘤免疫治疗。随着鉴定、分离和纯化技术的改进，外泌体有望成功应用于早期HCC的临床诊断和肝癌的临床治疗。
