Research progress on ferroptosis regulation in tumor immunity of hepatocellular carcinoma

Ferroptosis is a form of regulated cell death, which is dependent on iron metabolism imbalance and characterized by lipid peroxidation; it plays a crucial role in various pathological processes. Studies have shown that the occurrence of ferroptosis is closely associated with the progression of hepatocellular carcinoma (HCC). Ferroptosis is involved in regulating the lipid metabolism, iron homeostasis, mitochondrial metabolism, and redox processes in HCC. Additionally, ferroptosis plays a key role in HCC tumor immunity by modulating the phenotype and function of various immune cells in the tumor microenvironment, affecting tumor immune escape and progression. Ferroptosis-induced lipid peroxidation and oxidative stress can promote the polarization of M1 macrophages and enhance the pro-inflammatory response in tumors, inhibiting immune suppressive cells such as myeloid-derived suppressor cells and Treg cells to disrupt their immune suppression function. The expression regulation of ferroptosis-related molecules such as GPX4 and SLC7A11 not only affects the sensitivity of tumor cells to immunotherapy but also directly influences the activity and survival of effector cells such as T cells and dendritic cells, further enhancing or weakening host anti-tumor immune response. Targeting ferroptosis has demonstrated significant clinical potential in HCC treatment. Induction of ferroptosis by nanomedicine and molecular targeting strategies can directly kills tumor cells or enhances antitumor immune responses. The integration of multimodal therapies with immunotherapy further expands the application of targeting ferroptosis as a cancer therapy. This article reviews the relationship between ferroptosis and anti-tumor immune responses and the role of ferroptosis in HCC progression from the perspective of tumor immune microenvironment, to provide insights for the development of anti-tumor immune therapies based on targeting ferroptosis.