Unveiling the Yin-Yang Balance of M1 and M2 Macrophages in Hepatocellular Carcinoma: Role of Exosomes in Tumor Microenvironment and Immune Modulation
Stavros P. Papadakos, Nikolaos Machairas, Ioanna Ε. Stergiou, Konstantinos Arvanitakis, Georgios Germanidis, Adam E. Frampton, Stamatios Theocharis
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate and limited treatment options. Recent research has brought attention to the significant importance of intercellular communication in the progression of HCC, wherein exosomes have been identified as critical agents facilitating cell-to-cell signaling. In this article, we investigate the impact of macrophages as both sources and targets of exosomes in HCC, shedding light on the intricate interplay between exosome-mediated communication and macrophage involvement in HCC pathogenesis. It investigates how exosomes derived from HCC cells and other cell types within the tumor microenvironment (TME) can influence macrophage behavior, polarization, and recruitment. Furthermore, the section explores the reciprocal interactions between macrophage-derived exosomes and HCC cells, stromal cells, and other immune cells, elucidating their role in tumor growth, angiogenesis, metastasis, and immune evasion. The findings presented here contribute to a better understanding of the role of macrophage-derived exosomes in HCC progression and offer new avenues for targeted interventions and improved patient outcomes.