{"entity": "publication", "iuid": "31a742ddc95e40728e881f29e443ab69", "timestamp": "2026-08-23T09:27:27.573Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/31a742ddc95e40728e881f29e443ab69.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/31a742ddc95e40728e881f29e443ab69"}}, "title": "Identification of SPP1 + macrophages as an immune suppressor in hepatocellular carcinoma using single-cell and bulk transcriptomics.", "authors": [{"family": "Jin", "given": "Han", "initials": "H"}, {"family": "Kim", "given": "Woonghee", "initials": "W"}, {"family": "Yuan", "given": "Meng", "initials": "M"}, {"family": "Li", "given": "Xiangyu", "initials": "X"}, {"family": "Yang", "given": "Hong", "initials": "H"}, {"family": "Li", "given": "Mengzhen", "initials": "M"}, {"family": "Shi", "given": "Mengnan", "initials": "M"}, {"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Uhlen", "given": "Mathias", "initials": "M"}, {"family": "Zhang", "given": "Cheng", "initials": "C"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "journal article", "published": "2024-12-03", "journal": {"title": "Front Immunol", "issn": "1664-3224", "volume": "15", "pages": "1446453", "issn-l": "1664-3224"}, "abstract": "Macrophages and T cells play crucial roles in liver physiology, but their functional diversity in hepatocellular carcinoma (HCC) remains largely unknown.\n\nTwo bulk RNA-sequencing (RNA-seq) cohorts for HCC were analyzed using gene co-expression network analysis. Key gene modules and networks were mapped to single-cell RNA-sequencing (scRNA-seq) data of HCC. Cell type fraction of bulk RNA-seq data was estimated by deconvolution approach using single-cell RNA-sequencing data as a reference. Survival analysis was carried out to estimate the prognosis of different immune cell types in bulk RNA-seq cohorts. Cell-cell interaction analysis was performed to identify potential links between immune cell types in HCC.\n\nIn this study, we analyzed RNA-seq data from two large-scale HCC cohorts, revealing a major and consensus gene co-expression cluster with significant implications for immunosuppression. Notably, these genes exhibited higher enrichment in liver macrophages than T cells, as confirmed by scRNA-seq data from HCC patients. Integrative analysis of bulk and single-cell RNA-seq data pinpointed SPP1 + macrophages as an unfavorable cell type, while VCAN + macrophages, C1QA + macrophages, and CD8 + T cells were associated with a more favorable prognosis for HCC patients. Subsequent scRNA-seq investigations and in vitro experiments elucidated that SPP1, predominantly secreted by SPP1 + macrophages, inhibits CD8 + T cell proliferation. Finally, targeting SPP1 in tumor-associated macrophages through inhibition led to a shift towards a favorable phenotype.\n\nThis study underpins the potential of SPP1 as a translational target in immunotherapy for HCC.", "doi": "10.3389/fimmu.2024.1446453", "pmid": "39691723", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11649653"}], "notes": [], "created": "2026-08-20T13:06:53.725Z", "modified": "2026-08-20T13:06:53.738Z"}