Exosomes as mediators of tumor immune escape and immunotherapy in hepatocellular carcinoma

Hepatocellular carcinoma (HCC), a typical inflammatory-related cancer, mainly occurs in patients with chronic liver diseases. Moreover, the liver is an immunologically privileged apparatus with multiple immunosuppressive cell groups. The long process of inflammation-mediated carcinogenesis turns the HCC tumor microenvironment (TME) into one with strong immunosuppression, facilitating the immune escape of HCC cells. Accumulated data have manifested that tumor-associated cell-derived exosomes carry diverse molecular cargoes (e.g., proteins and nucleic acids) for mediating cell-to-cell communication and are implicated in TME remodeling to promote tumor-infiltrating immune cell reprogramming, ultimately creating a tumor-friendly microenvironment. Characterized by several intrinsic attributes, such as good stability (bilayer-like structure) and high biocompatibility (cell secretion), exosomes can be modified or engineered as nanocarriers to deliver tumor-specific antigens or antitumor drugs to targeted cells or organs, thus effectively triggering the HCC cell elimination by the immune system. This review aimed to highlight the pivotal role of exosomes in regulating immune escape mechanisms in HCC and recent advances in exosome-mediated immunotherapy for HCC.