Role of Exosomes in Immunotherapy of Hepatocellular Carcinoma.
Role of Exosomes in Immunotherapy of Hepatocellular Carcinoma.
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外泌体在肝细胞癌免疫治疗中的作用。
DOI：
10.3390/cancers14164036
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发表时间：
2022-08-21
期刊：
影响因子：
5.2
通讯作者：
Li, Tao
中科院分区：
文献类型：
--
作者：
Tian, Bao-Wen;Han, Cheng-Long;Dong, Zhao-Ru;Tan, Si-Yu;Wang, Dong-Xu;Li, Tao
关键词：
肝细胞癌是最致命的恶性肿瘤之一，预后极差。免疫治疗作为一种新兴的肿瘤治疗选择，为许多癌症患者带来了新的希望。然而，很大一部分患者没有从免疫治疗中受益。外泌体作为肿瘤免疫微环境中关键的细胞间通讯介质，可能在肝细胞癌免疫反应中发挥独特的作用，从而影响免疫治疗的效率。本文就外泌体在当前肝细胞癌免疫治疗耐药机制中作用的相关研究进行综述。此外，我们还阐明了外泌体出色的预测价值及其在提高肝细胞癌患者免疫治疗疗效中所发挥的作用。我们希望我们的综述能够帮助读者更全面地了解外泌体在肝细胞癌免疫治疗中的作用。肝细胞癌（HCC）是最致命的恶性肿瘤之一，预后极差，并且没有足够有效的治疗方法。免疫治疗，特别是免疫检查点抑制剂（ICIs）为HCC患者提供了新的治疗途径。然而，大多数 HCC 患者并未从免疫治疗中受益。外泌体是具有生物活性的脂质双层纳米级囊泡，尺寸范围为 30 至 150 nm，几乎可以由任何细胞分泌。在 HCC 肿瘤微环境 (TME) 中，许多细胞参与肿瘤进展，而源自肿瘤细胞和免疫细胞的外泌体表现出独特的组成特征，并通过运输各种物质充当细胞间通讯器。外泌体具有促进和抑制肿瘤的双重特性，在肿瘤细胞与周围免疫细胞之间的串扰中塑造肿瘤免疫反应，通过影响PD-1/PD-L1轴或TME中免疫细胞的抗肿瘤功能介导免疫治疗抵抗。靶向外泌体或应用外泌体作为疗法涉及 HCC 免疫疗法的许多方面（例如 ICI、肿瘤疫苗和过继性细胞疗法），并可能显着增强其疗效。在这篇综述中，我们讨论了外泌体对HCC TME的影响，并全面总结了外泌体在免疫治疗耐药和治疗应用中的作用。我们还讨论了外泌体作为预测免疫疗法疗效的生物标志物的潜力，以帮助临床医生识别适合免疫疗法的 HCC 患者。
Hepatocellular carcinoma is one of the most lethal malignancies, having a significantly poor prognosis. Immunotherapy, as an emerging tumor treatment option, provides new hope for many cancer patients. However, a large proportion of patients do not benefit from immunotherapy. As a critical cell-to-cell communication mediator in the tumor immune microenvironment, exosomes may play a unique role in hepatocellular carcinoma immune response and thus affect the efficiency of immunotherapy. In this review, we discuss related research on the roles of exosomes in the current immunotherapy resistance mechanism of hepatocellular carcinoma. Furthermore, we also clarify the excellent predictive value of exosomes and the roles they play in improving immunotherapy efficacy for hepatocellular carcinoma patients. We hope that our review can help readers to gain a more comprehensive understanding of exosomes’ roles in hepatocellular carcinoma immunotherapy. Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, having a significantly poor prognosis and no sufficiently efficient treatments. Immunotherapy, especially immune checkpoint inhibitors (ICIs), has provided new therapeutic approaches for HCC patients. Nevertheless, most patients with HCC do not benefit from immunotherapy. Exosomes are biologically active lipid bilayer nano-sized vesicles ranging in size from 30 to 150 nm and can be secreted by almost any cell. In the HCC tumor microenvironment (TME), numerous cells are involved in tumor progression, and exosomes—derived from tumor cells and immune cells—exhibit unique composition profiles and act as intercellular communicators by transporting various substances. Showing the dual characteristics of tumor promotion and suppression, exosomes exert multiple functions in shaping tumor immune responses in the crosstalk between tumor cells and surrounding immune cells, mediating immunotherapy resistance by affecting the PD-1/PD-L1 axis or the anti-tumor function of immune cells in the TME. Targeting exosomes or the application of exosomes as therapies is involved in many aspects of HCC immunotherapies (e.g., ICIs, tumor vaccines, and adoptive cell therapy) and may substantially enhance their efficacy. In this review, we discuss the impact of exosomes on the HCC TME and comprehensively summarize the role of exosomes in immunotherapy resistance and therapeutic application. We also discuss the potential of exosomes as biomarkers for predicting the efficacy of immunotherapy to help clinicians in identifying HCC patients who are amenable to immunotherapies.
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