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

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), therefore studying TAMs from different points of view passing by all the factors that may affect its existence, polarization, functions and repolarization are of great importance. Different epigenetic regulations were reported to have a direct relation with both HCC and TAMs. Here, this review discusses different epigenetic regulations that can affect TAMs in HCC whether positively or negatively.

Keywords: epigenetics; hepatocellular carcinoma (HCC); immunotherapy; macrophages; tumour-associated macrophages (TAMs).

Figure 1.

Origins of tissue-resident and TAMs. Tissue-resident macrophages are mainly derived from yolk sac during development. TAMs are derived from tissue-resident macrophages, or by differentiation of monocytes from the bone marrow. TAMs are polarized into M1-like or M2-like phenotypes based on signals received from the TME. HSPCs, haematopoietic stem cells and progenitor cells.

Figure 2.

Recruitment and polarization of macrophages. (1) TME different types of cells (DCs, macrophages, NK cells, fibroblasts). (2) Recruiting factors of macrophages towards TME, (3) Diverse polarization factors that affect the polarization of macrophages whether to M1 or alternatively M2, (4) Markers of M1, (5) Secretions of M1.

Figure 3.

Regulation of TAM polarization. (1) Different types of stimulators and suppressors of M2/TAM polarization (including LncRNAs, miRNAs, proteins, pathways, etc.). (2) Cellular markers. (3) Some factors that are secreted from M2/TAMs.