%0 Journal Article
%T Single-cell profiling reveals the metastasis-associated immune signature of hepatocellular carcinoma.
%A Zhong D
%A Shi Y
%A Ma W
%A Liang Y
%A Liu H
%A Qin Y
%A Zhang L
%A Yang Q
%A Huang X
%A Lu Y
%A Shang J
%J Immun Inflamm Dis
%V 12
%N 5
%D 2024 May
%M 38780041
%F 2.493
%R 10.1002/iid3.1264
%X <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.