{Reference Type}: Journal Article
{Title}: Single-cell profiling reveals the metastasis-associated immune signature of hepatocellular carcinoma.
{Author}: Zhong D;Shi Y;Ma W;Liang Y;Liu H;Qin Y;Zhang L;Yang Q;Huang X;Lu Y;Shang J;
{Journal}: Immun Inflamm Dis
{Volume}: 12
{Issue}: 5
{Year}: 2024 May
{Factor}: 2.493
{DOI}: 10.1002/iid3.1264
{Abstract}: <B>OBJECTIVE: </B>Metastasis is the leading cause of mortality in hepatocellular carcinoma (HCC). The metastasis-associated immune signature in HCC is worth exploring.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.