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

Author:

Papadakos Stavros P.1,Machairas Nikolaos2ORCID,Stergiou Ioanna E.3ORCID,Arvanitakis Konstantinos45ORCID,Germanidis Georgios45ORCID,Frampton Adam Enver678ORCID,Theocharis Stamatios1

Affiliation:

1. First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 10679 Athens, Greece

2. Second Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece

3. Pathophysiology Department, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece

4. Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, St. Kiriakidi 1, 54636 Thessaloniki, Greece

5. Basic and Translational Research Unit (BTRU), Special Unit for Biomedical Research and Education (BRESU), Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece

6. Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London W12 0NN, UK

7. Oncology Section, Surrey Cancer Research Institute, Department of Clinical and Experimental Medicine, FHMS, University of Surrey, The Leggett Building, Daphne Jackson Road, Guildford GU2 7WG, UK

8. HPB Surgical Unit, Royal Surrey NHS Foundation Trust, Guildford GU2 7XX, UK

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.

Publisher

MDPI AG

Subject

General Medicine

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