Bannister Megan E, Chatterjee Devnandan A, Shetty Shishir, Patten Daniel A
Centre for Liver and Gastrointestinal Research, School of Infection, Inflammation and Immunology, University of Birmingham, Birmingham B15 2TT, UK.
National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK.
Int J Mol Sci. 2024 Dec 7;25(23):13167. doi: 10.3390/ijms252313167.
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.
肝细胞癌（HCC）在全球范围内是一项重大的临床负担，并且预计在可预见的未来其发病率将持续上升。HCC的治疗因以下事实而变得复杂：在大多数情况下，它是在晚期慢性炎症性肝病的背景下发生的。慢性炎症可促进免疫抑制微环境，从而促进肿瘤进展和转移。在这种情况下，巨噬细胞构成了HCC肿瘤微环境的主要免疫成分，在本综述中，我们重点关注它们对HCC发生发展的作用。肿瘤相关巨噬细胞（TAM）主要来源于浸润的单核细胞，其强大的抗炎表型可由肿瘤微环境中存在的因素诱导，如生长因子、细胞因子、缺氧和细胞外基质（ECM）蛋白。一般来说，实验证据表明TAM可表现出多种有助于HCC肿瘤进展的功能，包括促进血管生成、对药物治疗的抗性以及释放支持肿瘤细胞增殖和转移的因子。尽管它们具有促进肿瘤的特性，但有证据表明这些细胞的潜在可塑性可成为靶点，以帮助重新编程TAM以驱动肿瘤特异性免疫反应。我们讨论了通过改变HCC微环境中TAM的表型或利用其从循环系统浸润到肿瘤组织的特性通过细胞治疗方法对TAM进行治疗靶向的潜力。
