Exosomes in hepatocellular carcinoma: involvement in reprogramming the tumor microenvironment for immune evasion, metastasis, angiogenesis, and drug resistance

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Abstract
Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer, and its progression is significantly influenced by the tumor microenvironment (TME). Tumor-derived exosomes (TEXs), an important component of the TME, significantly influence tumor growth by regulating immune responses, facilitating metastasis, and enhancing resistance to therapy. These extracellular vesicles (EVs) transport bioactive substances, such as proteins, lipids, and nucleic acids that promote interaction between cells in the TME. Recent research indicates that HCC-derived exosomes can inhibit immune cell activity, specifically in T cells, thus creating an immunosuppressive TME that facilitates tumor immune escape. They also augment metastatic capability by restructuring the extracellular matrix and promoting angiogenesis. Moreover, HCC-derived exosomes have been associated with developing resistance to drug therapy by transferring molecules such as apoptotic signals and oncogenic microRNAs, circRNAs and lncRNA. Understanding how HCC-derived exosomes affect immune modulation, metastasis, and drug resistance could yield innovative therapeutic targets to enhance therapy outcomes. This review focuses on recent research on the diverse functions of TEXs in HCC progression.

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