Caini Patrizio, Carloni Vinicio
Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy.
Biomedicines. 2025 Jun 13;13(6):1461. doi: 10.3390/biomedicines13061461.
Hepatocellular carcinoma (HCC) constitutes more than 90% of the primary tumor of the liver. Metabolic reprogramming is decisive in promoting HCC development. The new metabolic program drives the surrounding immune cells to an immune suppressive commitment, enabling tumor survival. The enhanced metabolic activity of cancer cells leads to competition for essential nutrients, depriving non-malignant cells of critical resources. Simultaneously, the accumulation of metabolic byproducts within the tumor microenvironment (TME) selectively favors innate immune responses while impairing adaptive immunity. Recent advances in cancer immunotherapy underscore the importance of targeting both immune cell function and metabolic pathways. In this context, reprogramming the metabolism of effector and regulatory immune cells represents a promising therapeutic avenue. This review focuses on a relatively underexplored aspect of liver cancer immunology, the immunosuppressive role of tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) driven by metabolic alterations and how these mechanisms contribute to the suppression of effective anti-tumor immune responses.
肝细胞癌（HCC）占原发性肝癌的90%以上。代谢重编程在促进HCC发展中起决定性作用。新的代谢程序促使周围免疫细胞向免疫抑制方向发展，从而使肿瘤得以存活。癌细胞代谢活性增强导致对必需营养物质的竞争，剥夺了非恶性细胞的关键资源。同时，肿瘤微环境（TME）中代谢副产物的积累选择性地有利于先天免疫反应，同时损害适应性免疫。癌症免疫治疗的最新进展凸显了靶向免疫细胞功能和代谢途径的重要性。在此背景下，重新编程效应免疫细胞和调节性免疫细胞的代谢代表了一条有前景的治疗途径。本综述聚焦于肝癌免疫学中一个相对未被充分探索的方面，即由代谢改变驱动的肿瘤相关巨噬细胞（TAM）和调节性T细胞（Treg）的免疫抑制作用，以及这些机制如何导致有效的抗肿瘤免疫反应受到抑制。
