Single‐cell profiling reveals the metastasis‐associated immune signature of hepatocellular carcinoma

Abstract

Abstract Aim Metastasis is the leading cause of mortality in hepatocellular carcinoma (HCC). The metastasis‐associated immune signature in HCC is worth exploring. Methods Bioinformatic analysis was conducted based on the single‐cell transcriptome data derived from HCC patients in different stages. Cellular composition, pseudotime state transition, and cell–cell interaction were further analyzed and verified. Results Generally, HCC with metastasis exhibited suppressive immune microenvironment, while HCC without metastasis exhibited active immune microenvironment. Concretely, effector regulatory T cells (eTregs) were found to be enriched in HCC with metastasis. PHLDA1 was identified as one of exhaustion‐specific genes and verified to be associated with worse prognosis in HCC patients. Moreover, A novel cluster of CCR7+ dendritic cells (DCs) was identified with high expression of maturation and migration marker genes. Pseudotime analysis showed that inhibition of differentiation occurred in CCR7+ DCs rather than cDC1 in HCC with metastasis. Furthermore, interaction analysis showed that the reduction of CCR7+ DCs lead to impaired CCR7/CCL19 interaction in HCC with metastasis. Conclusions HCC with metastasis exhibited upregulation of exhaustion‐specific genes of eTregs and inhibition of CCL signal of a novel DC cluster, which added new dimensions to the immune landscape and provided new immune therapeutic targets in advanced HCC.

Keywords

• dendritic cells
• hepatocellular carcinoma
• metastasis
• single cell RNA sequencing
• Treg cells
• tumor immune microenvironment