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基于外泌体的肝细胞癌免疫治疗

Exosome-based immunotherapy in hepatocellular carcinoma.

作者信息

Liu Hong, Wang GuoWei, Li ZhaoYi, Zhang XianTu, Zhang WeiDong, Zhang Xia, Liu Fang, Gao Jing

机构信息

Department of Pathology, Xixi Hospital of Hangzhou, Hangzhou, 310023, Zhejiang Province, China.

Department of Radiology, Xixi Hospital of Hangzhou, Hangzhou, 310023, Zhejiang Province, China.

出版信息

Clin Exp Med. 2025 Apr 24;25(1):127. doi: 10.1007/s10238-025-01659-2.


DOI:10.1007/s10238-025-01659-2
PMID:40274634
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12021721/
Abstract

Hepatocellular carcinoma (HCC) is a significant global health concern and ranks as the third leading cause of cancer-associated mortality. Systemic therapy faces the emergence of resistance, which hinders the clinical benefits. Recent evidence suggests that exosomes, measuring between 30 and 150 nm in size, which impact the antitumor immune responses, making them a promising candidate for cancer immunotherapy. Owing to their unique physical and chemical characteristics, exosomes can be tailored and engineered for a range of therapeutic objectives. In the present review, we outline the immunomodulatory functions of exosomes in the tumor microenvironment (TME) of HCC, aiming to decipher the underlying mechanisms of exosomes in remodeling suppressive TME. Moreover, we provide detailed and intuitive resource for leveraging the potential of exosomes in immunotherapy, presenting valuable strategies to improve and optimize HCC treatment. Despite the huge therapeutic potential of exosomes, significant challenges persist, including the need for standardization in exosome production, optimization of cargo loading techniques, and the assurance of safety and effectiveness in clinical applications. Addressing these challenges may pave the way for exosome-based immunotherapy for HCC patients.

摘要

肝细胞癌(HCC)是一个重大的全球健康问题,是癌症相关死亡的第三大主要原因。全身治疗面临耐药性的出现,这阻碍了临床疗效。最近的证据表明,大小在30至150纳米之间的外泌体影响抗肿瘤免疫反应,使其成为癌症免疫治疗的一个有前景的候选者。由于其独特的物理和化学特性,外泌体可以针对一系列治疗目标进行定制和工程改造。在本综述中,我们概述了外泌体在HCC肿瘤微环境(TME)中的免疫调节功能,旨在解读外泌体重塑抑制性TME的潜在机制。此外,我们为利用外泌体在免疫治疗中的潜力提供详细而直观的资源,提出改进和优化HCC治疗的有价值策略。尽管外泌体具有巨大的治疗潜力,但重大挑战依然存在,包括外泌体生产的标准化需求、货物装载技术的优化以及临床应用中安全性和有效性的保证。应对这些挑战可能为HCC患者基于外泌体的免疫治疗铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e71/12021721/4a908a919352/10238_2025_1659_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e71/12021721/a19517c146c9/10238_2025_1659_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e71/12021721/2f1585b34e52/10238_2025_1659_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e71/12021721/4a908a919352/10238_2025_1659_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e71/12021721/a19517c146c9/10238_2025_1659_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e71/12021721/2f1585b34e52/10238_2025_1659_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e71/12021721/4a908a919352/10238_2025_1659_Fig3_HTML.jpg

相似文献

[1]
Exosome-based immunotherapy in hepatocellular carcinoma.

Clin Exp Med. 2025-4-24

[2]
Crosstalk between exosomes and tumor-associated macrophages in hepatocellular carcinoma: implication for cancer progression and therapy.

Front Immunol. 2025-4-8

[3]
Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression.

J Hematol Oncol. 2019-5-29

[4]
Cancer-associated fibroblasts in hepatocellular carcinoma: heterogeneity, mechanisms and therapeutic targets.

Hepatol Int. 2025-4

[5]
From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma.

J Exp Clin Cancer Res. 2019-9-9

[6]
The role of exosomes in liver cancer: comprehensive insights from biological function to therapeutic applications.

Front Immunol. 2024

[7]
Recent progress in the emerging role of exosome in hepatocellular carcinoma.

Cell Prolif. 2018-11-5

[8]
Dual-Synergistic Nanomodulator Alleviates Exosomal PD-L1 Expression Enabling Exhausted Cytotoxic T Lymphocytes Rejuvenation for Potentiated iRFA-Treated Hepatocellular Carcinoma Immunotherapy.

ACS Nano. 2024-11-26

[9]
CXCL12 tumor-associated endothelial cells promote immune resistance in hepatocellular carcinoma.

J Hepatol. 2025-4

[10]
Role of exosomes and exosomal microRNAs in hepatocellular carcinoma: Potential in diagnosis and antitumour treatments (Review).

Int J Mol Med. 2018-1-11

本文引用的文献

[1]
Artificial Intelligence Transforming Post-Translational Modification Research.

Bioengineering (Basel). 2024-12-31

[2]
Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems.

Bioengineering (Basel). 2024-11-23

[3]
Cellular senescence offers distinct immunological vulnerabilities in cancer.

Trends Cancer. 2025-4

[4]
Turning cold into hot: emerging strategies to fire up the tumor microenvironment.

Trends Cancer. 2025-2

[5]
Could intratumoural microbiota be key to unlocking treatment responses in hepatocellular carcinoma?

Eur J Cancer. 2025-2-5

[6]
M2-polarized tumor-associated macrophage-secreted exosomal lncRNA NEAT1 upregulates galectin-3 by recruiting KLF5 and promotes HCC immune escape.

J Cell Commun Signal. 2024-12-23

[7]
Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives.

J Hematol Oncol. 2024-12-21

[8]
Optimal timing of anti-PD-1 antibody combined with chemotherapy administration in patients with NSCLC.

J Immunother Cancer. 2024-12-19

[9]
myCAF-derived exosomal PWAR6 accelerates CRC liver metastasis via altering glutamine availability and NK cell function in the tumor microenvironment.

J Hematol Oncol. 2024-12-18

[10]
Enhancing the anti-tumor activity and reprogramming M2 macrophages by delivering siRNAs against SIRPα and STAT6 via M1 exosomes and combining with anti-PD-L1.

Life Sci. 2025-1-15

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