Zhang Xiang, Zhang Cheng, Zhang Zheng, Zhang Xuan
School of Anesthesiology, Wannan Medical College, Wuhu, Anhui, China.
School of Clinical Medicine, Wannan Medical College, Wuhu, Anhui, China.
Front Immunol. 2025 Aug 13;16:1628573. doi: 10.3389/fimmu.2025.1628573. eCollection 2025.
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy, whose progression is intimately linked to the complex dynamics of the tumor microenvironment (TME). Exosomes, once considered mere cellular waste, have emerged as pivotal mediators of intercellular communication within the TME, actively participating in the multistep development of HCC. These nanoscale vesicles play crucial roles in the initiation of precancerous lesions and, by transporting drug resistance-related molecules such as proteins and non-coding RNAs, facilitate the acquisition of resistance to chemotherapy and targeted therapies by tumor cells. Moreover, exosomes contribute to the establishment of pre-metastatic niches by remodeling distant organ microenvironments-inducing hypoxia, metabolic reprogramming, and angiogenesis-which collectively create favorable conditions for tumor cell colonization. They also modulate immune responses by inducing T-cell exhaustion, promoting macrophage polarization, and disrupting normal stromal cell functions, thereby constructing an immunosuppressive microenvironment that enables tumor immune evasion. Given their inherent biocompatibility and targeting capabilities, engineered exosomes have shown promise in cancer therapy, serving as carriers for therapeutic molecules and enabling precise drug delivery through surface modifications. Despite significant advancements, challenges remain in elucidating the regulatory mechanisms of exosomes, standardizing their isolation and purification processes, and evaluating their clinical efficacy. This review examines the multifaceted roles of exosomes in HCC, aiming to bridge mechanistic insights with precision diagnostics and pave new avenues for liver cancer treatment.
肝细胞癌(HCC)是一种高度侵袭性的恶性肿瘤,其进展与肿瘤微环境(TME)的复杂动态密切相关。外泌体曾被认为只是细胞废物,现已成为TME内细胞间通讯的关键介质,积极参与HCC的多步骤发展。这些纳米级囊泡在癌前病变的起始中起关键作用,并通过运输蛋白质和非编码RNA等与耐药相关的分子,促进肿瘤细胞获得对化疗和靶向治疗的耐药性。此外,外泌体通过重塑远处器官微环境——诱导缺氧、代谢重编程和血管生成——有助于建立前转移生态位,这些共同为肿瘤细胞定植创造有利条件。它们还通过诱导T细胞耗竭、促进巨噬细胞极化和破坏正常基质细胞功能来调节免疫反应,从而构建一个能够实现肿瘤免疫逃逸的免疫抑制微环境。鉴于其固有的生物相容性和靶向能力,工程化外泌体在癌症治疗中显示出前景,可作为治疗分子的载体,并通过表面修饰实现精确给药。尽管取得了重大进展,但在阐明外泌体的调控机制、规范其分离和纯化过程以及评估其临床疗效方面仍存在挑战。本综述探讨了外泌体在HCC中的多方面作用,旨在将机制见解与精准诊断联系起来,为肝癌治疗开辟新途径。
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