Epigenetic tuning of tumour-associated macrophages (TAMs): a potential approach in hepatocellular carcinoma (HCC) immunotherapy

Sep 21, 2026

Uploaded by Rowan

Recent development in immunotherapy for cancer treatment has shown stronger effectiveness than many other modalities. Cancer can subvert immune compartments to support tumour progression, and tumour-associated macrophages (TAMs), a dominant tumour microenvironment component, act as anti-tumour suppressors. Yet TAM behaviour remains insufficiently defined and understudied. TAM density relates to hepatocellular carcinoma progression and prognosis, making study of TAM existence, polarization, functions and repolarization critical. This review evaluates epigenetic regulations that modulate TAMs in HCC, including beneficial and adverse effects.

LanguageEnglish

CategoryResearch & Report

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Pages19

Reading Time48 min

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Abstract

Introduction

Expert Reviews in Molecular Medicine [cambridge.org/erm](cambridge.org/erm) Review Cite this article: Helal IM, Kamal MA, Abd ElAziz MK, El Tayebi HM (2024) . Epigenetic tuning of tumour-associated macrophages (TAMs): a potential approach in hepatocellular carcinoma (HCC) immunotherapy. Expert Reviews in Molecular Medicine 26, e18, 1–19. [https://doi.org/10.1017/erm.2024.9](https://doi.org/10.1017/erm.2024.9) Received: 7 June 2023 Revised: 21 January 2024 Accepted: 26 February 2024 Keywords: epigenetics; hepatocellular carcinoma (HCC); immunotherapy; macrophages; tumourassociated macrophages (TAMs) Abbreviations: ARID: AT-rich interaction domain; CIITA: class II transactivator; CT: cryptotanshinone; DC: dendritic cell; DNMT: DNA methyltransferase; EMT: epithelial–mesenchymal transition; EZH2: enhancer of Zeste homologue-2; FcγR: Fcγ receptor; GBM: glioblastoma multi-form; H3K4: histone 3 lysine 4; HCC: hepatocellular carcinoma; HDAC: histone deacetylase; HIF: hypoxia-inducible factor; IC: immune complex; IGF-II: insulin-like growth factor-II; IGF-1R: insulin-like growth factor type-1 receptor; IGFBP-3: insulin-like growth factor binding protein-3; IL: interleukin; IL-1R: interleukin-1 receptor; KC: Kupffer cell; LLC: Lewis lung cancer; LncRNA: long non-coding RNA; m1A: N1-methyladenosine, m6A, N6- methyladenosine, m5C, 5-methylcytosine; miR-98: microRNA 98; miRNA: microRNA; mtDNA: mitochondrial DNA; MHC II: major histocompatibility complex class II; MIAT: myocardial infarction associated transcript; MMP9: matrix metallopeptidase 9; ncRNA: non-coding RNA; NF-κB: nuclear factor kappa B; NK: natural killer; NLR: neutrophil-tolymphocyte ratio; NOR1: nitro domain containing protein 1; PBRM1: polybromo 1; PRMT1: protein arginine methyltransferase 1; qRT-PCR: quantitative real-time polymerase chain reaction; STAT: signal transducer and activator of transcription; SMARCA4: SWI/SNFrelated, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4; SWI/SNF: switch/sucrose non-fermenting; TACE: trans-arterial chemoembolization; TAM: tumour-associated macrophage; TAN: tumourassociated neutrophil; TGF-β: transforming growth factor-beta; TLR: Toll-like receptor; TME: tumour microenvironment; TNF-α: tumour necrosis factor-alpha; T-UCR: transcribed ultra-conserved region; VEGF: vascular endothelial growth factor; YAP: Yesassociated protein Corresponding author: HendM. El Tayebi; [Email:](Email: hend.saber@guc.edu.eg)[ hend.saber@guc.edu.eg](Email: hend.saber@guc.edu.eg) © The Author(s), 2024 . Published by Cambridge University Press. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited. Epigenetic tuning of tumour-associated macrophages (TAMs): a potential approach in hepatocellular carcinoma (HCC) immunotherapy Israa M. Helal, Monica A. Kamal, Mostafa K. Abd El-Aziz and Hend M. El Tayebi Clinical Pharmacology and Pharmacogenomics Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo - GUC, Cairo, Egypt Abstract Recent development in immunotherapy for cancer treatment has substantiated to be more effective than most of the other treatments. Immunity is the first line of defence of the body; nevertheless, cancerous cells can manipulate immunity compartments to play several roles in tumour progression. Tumour-associated macrophages (TAMs), one of the most dominant components in the tumour microenvironment, are recognized as anti-tumour suppressors. Unfortunately, the complete behaviour of TAMs is still unclear and understudied. TAM density is directly correlated with the progression and poor prognosis of hepatocellular carcinoma (HCC), therefor

FAQs

What role do tumour-associated macrophages (TAMs) play in hepatocellular carcinoma?

TAMs are a dominant component of the tumour microenvironment. They are described as anti-tumour suppressors, and their density correlates with HCC progression and poor prognosis.

Why is studying TAMs from different perspectives important?

Because TAM behaviour is still unclear and understudied. Examining factors affecting TAM existence, polarization, functions, and repolarization is considered critical.

How do epigenetic regulations relate to TAMs and HCC?

Reported epigenetic regulations have direct relationships with both HCC and TAMs. The review discusses epigenetic mechanisms that can influence TAMs in HCC, with potential positive or negative effects.

Sep 21, 2026

Uploaded by Rowan