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The fibroblast-centered cellular crosstalk in HBV-positive liver cancer revealed by single cell sequencing

ABSTRACT: Here, we generated full-length single cell transcriptome data for ~9,000 cells from clinical samples of 11 liver cancer patients to delineate cellular relationships of diverse malignant, immune and stromal cells. We identified an immunomodulatory fibroblast population, FAP+CCL19+CCL21+ CAFs, that expressed signatures of fibroblastic reticular cells and was associated with favorable prognosis in hepatocellular carcinoma (HCC). These CAFs exhibited the potential to recruit NK cells and regulate tumor-associated macrophages, and appeared to be regulated by CXCL12+ endothelial cells in tumors through specific ligand-receptor interaction. Further, we uncovered clonal HBV integration events enriched in tumor cells, and trajectory analysis on tumor cells with clonal HBV integration events revealed that hepatoblast-like cells differentiated into a terminal state with high expression of an immune-resistance program. The intercellular crosstalks between CAFs and cancer cells, macrophages, and NK cells, combined with HBV-based lineage tracing, provide a better understanding for functional roles of CAFs in the HCC microenvironment, and the relationship between HBV integration and liver malignancies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE189935 | GEO | 2023/12/31

REPOSITORIES: GEO

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