REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1628573
This article is part of the Research TopicCommunity Series in Biomarkers in the Era of Cancer Immunotherapy: Zooming in from Periphery to Tumor Microenvironment, Volume IIIView all 7 articles
Multidimensional Insights into Exosomes in Hepatocellular Carcinoma: From Genesis to Clinical Application
Provisionally accepted
- 1Wannan Medical College, Wuhu, China
- 2Bengbu Medical University, Bengbu, China
- 3Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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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 microenvironmentsinducing 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 in vivo 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.
Keywords: hepatocellular carcinoma (HCC )1, exosomes2, tumor microenvironment (TME)3, drug tolerance4, Metastasis5, targeted therapy6
Received: 14 May 2025; Accepted: 25 Jul 2025.
Copyright: © 2025 Zhang, Cheng, Zhang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiang Zhang, Wannan Medical College, Wuhu, China
Zheng Zhang, Bengbu Medical University, Bengbu, China
Xuan Zhang, Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.