Unveiling the Yin-Yang Balance of M1 and M2 Macrophages in Hepatocellular Carcinoma: Role of Exosomes in Tumor Microenvironment and Immune Modulation

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.

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

“…The therapeutic potential of EVs in HCC is a subject of increasing scientific interest and holds promise for innovative diagnostic and therapeutic interventions [32,143,144]. 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 lipid A moiety is a biologically active component EVs fulfill a wide spectrum of biological functions, participating in various physiological and pathological processes [12,13]. When facilitating intercellular communication by transferring a diverse array of molecules between cells, EVs play pivotal roles in intricate biological events like tumorigenesis [6], the formation of pre-metastatic niches [14], inflammation, and immune modulation [15]. Their composition reflecting the state of the parent cell during production renders them promising candidates for diagnostics [16,17].…”

Crosstalk between Epigenetics and Metabolic Reprogramming in Metabolic Dysfunction-Associated Steatotic Liver Disease-Induced Hepatocellular Carcinoma: A New Sight

“…By ensuring that patients are receiving enough calories and nutrients, healthcare professionals can help improve treatment outcomes and overall quality of life for individuals battling HCC [ 250 ]. However, the majority of MASLD-HCC is diagnosed at an advanced stage, making systemic therapy the only option [ 251 , 252 ]. Although immunotherapy has been approved for the treatment of MASLD-related HCC, emerging evidence suggests that this specific subset of patients may not respond well to this treatment option [ 253 ].…”

Meeting at the Crossroad between Obesity and Hepatic Carcinogenesis: Unique Pathophysiological Pathways Raise Expectations for Innovative Therapeutic Approaches

“…For later stages of HCC, systemic drug administration is the treatment of choice [16,65,121]. Sorafenib, a tyrosine kinase inhibitor, was the drug of choice for HCC for several years [16,65,149], but various other novel therapeutic options have been approved [16,65,119,150,151]. Overall, upon evaluating and deciding on available treatment options for patients with HCC, a thorough assessment by multidisciplinary teams in experienced centers should be performed, and the most suitable therapy for each patient should be considered via constant re-evaluation [16,65].…”