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Review

The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential

by
Megan E. Bannister
1,
Devnandan A. Chatterjee
1,2,
Shishir Shetty
1,2,*,† and
Daniel A. Patten
1,*,†
1
Centre for Liver and Gastrointestinal Research, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham B15 2TT, UK
2
National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK
*
Authors to whom correspondence should be addressed.
Indicates joint senior authors.
Int. J. Mol. Sci. 2024, 25(23), 13167; https://doi.org/10.3390/ijms252313167
Submission received: 14 October 2024 / Revised: 5 December 2024 / Accepted: 6 December 2024 / Published: 7 December 2024

Abstract

Hepatocellular carcinoma (HCC) represents a significant clinical burden globally and is predicted to continue to increase in incidence for the foreseeable future. The treatment of HCC is complicated by the fact that, in the majority of cases, it develops on a background of advanced chronic inflammatory liver disease. Chronic inflammation can foster an immunosuppressive microenvironment that promotes tumour progression and metastasis. In this setting, macrophages make up a major immune component of the HCC tumour microenvironment, and in this review, we focus on their contribution to HCC development and progression. Tumour-associated macrophages (TAMs) are largely derived from infiltrating monocytes and their potent anti-inflammatory phenotype can be induced by factors that are found within the tumour microenvironment, such as growth factors, cytokines, hypoxia, and extracellular matrix (ECM) proteins. In general, experimental evidence suggest that TAMs can exhibit a variety of functions that aid HCC tumour progression, including the promotion of angiogenesis, resistance to drug therapy, and releasing factors that support tumour cell proliferation and metastasis. Despite their tumour-promoting profile, there is evidence that the underlying plasticity of these cells can be targeted to help reprogramme TAMs to drive tumour-specific immune responses. We discuss the potential for targeting TAMs therapeutically either by altering their phenotype within the HCC microenvironment or by cell therapy approaches by taking advantage of their infiltrative properties from the circulation into tumour tissue.
Keywords: hepatocellular carcinoma; macrophages; TAMs; tumour microenvironment hepatocellular carcinoma; macrophages; TAMs; tumour microenvironment

Share and Cite

MDPI and ACS Style

Bannister, M.E.; Chatterjee, D.A.; Shetty, S.; Patten, D.A. The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential. Int. J. Mol. Sci. 2024, 25, 13167. https://doi.org/10.3390/ijms252313167

AMA Style

Bannister ME, Chatterjee DA, Shetty S, Patten DA. The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential. International Journal of Molecular Sciences. 2024; 25(23):13167. https://doi.org/10.3390/ijms252313167

Chicago/Turabian Style

Bannister, Megan E., Devnandan A. Chatterjee, Shishir Shetty, and Daniel A. Patten. 2024. "The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential" International Journal of Molecular Sciences 25, no. 23: 13167. https://doi.org/10.3390/ijms252313167

APA Style

Bannister, M. E., Chatterjee, D. A., Shetty, S., & Patten, D. A. (2024). The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential. International Journal of Molecular Sciences, 25(23), 13167. https://doi.org/10.3390/ijms252313167

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