Roles of tumor associated neutrophils in the development of hepatocellular carcinoma and therapeutic implications

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death globally, with limited clinical response to conventional therapies and emerging immune checkpoint inhibitors, such as Programmed death receptor-1/programmed death receptor ligand-1 (PD-1/PD-L1) antibodies. In recent years, immunomodulatory cells in the tumor microenvironment (TME) have become a focus of research. Among these, tumor-associated neutrophils (TANs) have been found to play a key role in HCC progression by modulating immune suppression, promoting angiogenesis and facilitating tumor metastasis. Although the role of TANs in various cancers has been extensively studied, systematic reviews on their heterogeneous functions and regulatory mechanisms in HCC remain scarce, and existing studies have yet to comprehensively integrate targeted therapeutic strategies. Therefore, this review aims to fill this research gap by systematically summarizing the current advancements in understanding the origin and functional roles of TANs in HCC, while emphasizing emerging TANs-centered therapeutic strategies to improve immune treatment efficacy and achieve more precise interventions.