Single-cell dissection of hepatocellular carcinoma immunity: from heterogeneous subtypes to precision therapeutics

Hepatocellular carcinoma (HCC) represents one of the most prevalent malignancies worldwide and poses a critical public health challenge due to difficulties in early diagnosis, therapy resistance, and high mortality rates. The complex tumor microenvironment (TME) of HCC plays a pivotal role in tumor progression, immune evasion, metastasis, and treatment resistance. Single-cell sequencing (scRNA-seq) has emerged as a revolutionary tool for resolving the intricacies and cellular heterogeneity of the TME, with its applications in advancing therapeutic research attracting considerable attention. As the primary battleground for antitumor immune responses, the HCC tumor TME warrants comprehensive analysis of immune cell subsets at distinct developmental and functional states to elucidate the complexity of tumor immunology. This review synthesizes extensive research on TME immune cellular subpopulations, in order to summarize mainstream classifications of immune subsets at single-cell resolution and analyze their functional significance and therapeutic value through biomarker gene profiling.