Exosome-mediated Crosstalk in the Tumor Immune Microenvironment: Critical Drivers of Hepatocellular Carcinoma Progression

Abstract

Hepatocellular carcinoma (HCC) is a significant global health issue, ranking as the sixth most prevalent malignancy and the fourth leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, mortality rates for HCC remain high. The tumor immune microenvironment (TIME) plays a vital role in HCC progression by influencing tumor cell survival and growth. Recent studies highlight the essential role of exosomes in mediating intercellular communication within the TIME, particularly in interactions among tumor cells, immune cells, and fibroblasts. These interactions drive critical aspects of tumor development, including immune escape, angiogenesis, drug resistance, and metastasis. A detailed understanding of the molecular mechanisms by which exosomes modulate the TIME is essential for developing targeted therapies. This review systematically evaluated the roles and regulatory mechanisms of exosomes within the TIME of HCC, examining the impact of both HCC-derived and non-HCC-derived exosomes on various cellular components within the TIME. It emphasized their regulatory effects on cell phenotypes and functions, as well as their roles in HCC progression. The review also explored the potential applications of exosome-based immunotherapies, offering new insights into improving therapeutic strategies for HCC.