Role of exosomes in the development of the immune microenvironment in hepatocellular carcinoma

Abstract

Despite numerous improved treatment methods used in recent years, hepatocellular carcinoma (HCC) is still a disease with a high mortality rate. Many recent studies have shown that immunotherapy has great potential for cancer treatment. Exosomes play a significant role in negatively regulating the immune system in HCC. Understanding how these exosomes play a role in innate and adaptive immunity in HCC can significantly improve the immunotherapeutic effects on HCC. Further, engineered exosomes can deliver different drugs and RNA molecules to regulate the immune microenvironment of HCC by regulating the aforementioned immune pathway, thereby significantly improving the mortality rate of HCC. This study aimed to declare the role of exosomes in the development of the immune microenvironment in HCC and list engineered exosomes that could be used for clinical transformation therapy. These findings might be beneficial for clinical patients.

Exosome Cargos as Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma

“…They play a crucial role in the physiological processes of cellular formation, growth, differentiation, and aging in human cells, particularly in relation to the development, metastasis, and progression of cancer [ 20 ]. Numerous studies have substantiated the exact regulation of exosome synthesis, secretion, transport, uptake, and release through unique signaling pathways, which in turn exert an influence on the growth and immunosuppression of HCC [ 21 ]. In this section, we explore the mechanisms by which HCC cells generate and release exosomes to facilitate intercellular communication and modulate microenvironmental conditions, as well as the composition and functions of these extracellular vesicles ( Figure 1 ).…”

“…However, in cancer tissue, tumor cells possess the ability to deceive immune cells and escape immune surveillance, resulting in immunosuppression and cancer development [ 49 ]. The effects of exosomes on HCC encompass decreasing immune cell activity, facilitating the apoptosis of CD8+ T lymphocytes, eliciting the activation of regulatory T cells (Tregs), and leading to Th17/Treg imbalance [ 1 , 12 , 21 , 24 ]. Several studies found that the highly abundant exosomal 14-3-3 ζ protein can inhibit the activation, proliferation, and differentiation of T cells, inducing their transformation into Tregs, which causes protumor immune response [ 50 ].…”

Interplay of Extracellular Vesicles and TLR4 Signaling in Hepatocellular Carcinoma Pathophysiology and Therapeutics

“…Within the context of HCC, EVs have emerged as key players in the intricate network of intercellular communication within the tumor microenvironment [15,145,146]. These vesicles carry a cargo of bioactive molecules with the capacity to profoundly influence various aspects of HCC progression [109], encompassing tumor growth [147], immune evasion mechanisms [148,149], and resistance to therapeutic interventions. The distinctive composition of EV cargo, enriched with HCC-specific biomolecules, offers an attractive avenue for targeted therapeutic strategies [11].…”

An emerging research: the role of hepatocellular carcinoma-derived exosomal circRNAs in the immune microenvironment

“…Exosomal circRNAs have been reported to reshape the tumor microenvironment by prompting hypoxic stress response, stimulating angiogenesis ( 36 ), contributing to metabolic reprogramming ( 37 , 38 ), facilitating inflammatory changes in the HCC cells ( 39 ) and inducing tumor immunosuppression. The exosomes secreted by HCC cells carry circRNA into immune cells, which intervene in the activation of immune cells and promote the overexpression of immune checkpoints to regulate immune response, leading tumor cells to acquire immunosuppressive properties ( 40 ). Furthermore, immunosuppression is the final result of a combination of TME-related factors, including hypoxia, angiogenesis, metabolic reprogramming, and inflammation changes.…”