Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Since most patients with HCC are diagnosed at the intermediate or advanced stage and because HCC has a high incidence of metastasis and recurrence, it is one of the leading causes of cancer death. Exosomes are a subtype of extracellular vesicles and are typically 30–150 nm in diameter. Originating from endosomes, they can be secreted by almost all living cells. They are widely present in various body fluids and serve as an important medium for the interactions between cells. A series of studies have revealed that exosomes-mediated intercellular transfer of proteins, nucleic acids, and metabolites plays a crucial role in the initiation and progression of HCC, hypoxia and angiogenesis, chemotherapy sensitivity, and cell death mode and regulates the immune microenvironment. In this paper, we reviewed the recent researches on the multiple roles of tumor-associated exosomes in the progression of HCC. We laid particular focus on those researches that reveal how exosomes regulate the tumor immune microenvironment (TIME) and how exosomal cargos affect the progression of HCC. Besides, we emphasize some prospective directions to achieve a more accurate and complete analysis of the HCC immune microenvironment.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third most fatal cancer [1]
Whereas exosomes in the blood are derived from multitissue cells, the exosomes secreted by the cells exist first and foremost in interstitial space, which means that tissue-derived exosomes can better reveal the tumor microenvironment
We introduce several in-depth studies of hypoxia, angiogenesis, epithelial-to-mesenchymal transition (EMT), chemotherapy sensitivity, etc. and discuss the various roles that exosomal miRNAs can play under different conditions
Summary
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third most fatal cancer [1]. Is is associated with the formation of the HCC immunosuppressive microenvironment which seriously hinders the antitumor effect of immune checkpoint inhibitors, attenuating the efficacy of immunotherapy [2]. Regardless of the type or the physiological or pathological state of the originating cell, exosomes share common features as enriched with nucleic acids, lipids, and proteins [4]. The specific exosomal composition depends to some extent on the cell type and is affected by different cell conditions or treatments. Exosomes act as a signal-transmitting medium between cells to mediate intercellular communication and change the functional status of recipient cells [11]. HCC-derived exosomes participate in changing tumor progression by regulating the tumor microenvironment and tumor immune status [14,15]. Erefore, the current research focuses on the interaction between exosomes and immune cells in HCC HCC-derived exosomes participate in changing tumor progression by regulating the tumor microenvironment and tumor immune status [14,15]. erefore, the current research focuses on the interaction between exosomes and immune cells in HCC
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