{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14(2)"],"submitter":["Lian SL"],"pubmed_abstract":["The inflammation-related tumor microenvironment (TME) is one of the major driving forces of hepatocarcinogenesis. We aimed to investigate cell-to-cell communication among Hepatocellular Carcinoma (HCC) through re-analyzing HCC single-cell RNA-seq data, and to confirm such cellular interaction through <i>in vitro</i> and <i>in vivo</i> study. We found a subset of Regulatory B cells with PD-L1 expression (PD-L1<sup>+</sup> Bregs), mainly located in adjacent HCC tissues. In co-localization with PD-L1<sup>+</sup> Bregs, a subset of Tumor Associated Macrophages with high expression of CXCL12 (CXCL12<sup>+</sup> TAMs) was also mainly located in adjacent HCC tissues. Moreover, CXCL12<sup>+</sup> TAMs can be stimulated <i>in vitro</i> using an HCC conditional medium. Using CellChat analysis and Multiplex Immunohistochemistry staining (mIHC), CXCL12<sup>+</sup> TAMs were found to be first recruited by Cancer-Associated Fibroblasts (CAFs) through a CD74/macrophage migration inhibitory factor (MIF) pattern, and further differentiated into TGF-β-enriched tissues. Furthermore, CXCL12<sup>+</sup> TAMs recruited PD-L1<sup>+</sup> Bregs via the CXCL12/CXCR4 axis, and CXCR4 expression was significantly positively correlated to PD-L1 expression in PD-L1<sup>+</sup> Bregs. At last, we confirmed the communications among CAFs, Macrophages and B cells and their tumor-promoting effects by using an orthotopic mouse model of HCC. Immunosuppressive HCC TME involving cell-to-cell communications comprised MIF-secreting CAFs, CXCL12-secreting TAMs, and PD-L1-producing Bregs, and their regulation could be promising therapeutic targets in future immunotherapy for human HCC."],"journal":["American journal of cancer research"],"pagination":["832-853"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10915331"],"repository":["biostudies-literature"],"pubmed_title":["Tumor-associated macrophages promoting PD-L1 expression in infiltrating B cells through the CXCL12/CXCR4 axis in human hepatocellular carcinoma."],"pmcid":["PMC10915331"],"pubmed_authors":["Lian SL","Wang XL","Yao YL","Lu YT","Lu YJ","Jiang RQ"],"additional_accession":[]},"is_claimable":false,"name":"Tumor-associated macrophages promoting PD-L1 expression in infiltrating B cells through the CXCL12/CXCR4 axis in human hepatocellular carcinoma.","description":"The inflammation-related tumor microenvironment (TME) is one of the major driving forces of hepatocarcinogenesis. We aimed to investigate cell-to-cell communication among Hepatocellular Carcinoma (HCC) through re-analyzing HCC single-cell RNA-seq data, and to confirm such cellular interaction through <i>in vitro</i> and <i>in vivo</i> study. We found a subset of Regulatory B cells with PD-L1 expression (PD-L1<sup>+</sup> Bregs), mainly located in adjacent HCC tissues. In co-localization with PD-L1<sup>+</sup> Bregs, a subset of Tumor Associated Macrophages with high expression of CXCL12 (CXCL12<sup>+</sup> TAMs) was also mainly located in adjacent HCC tissues. Moreover, CXCL12<sup>+</sup> TAMs can be stimulated <i>in vitro</i> using an HCC conditional medium. Using CellChat analysis and Multiplex Immunohistochemistry staining (mIHC), CXCL12<sup>+</sup> TAMs were found to be first recruited by Cancer-Associated Fibroblasts (CAFs) through a CD74/macrophage migration inhibitory factor (MIF) pattern, and further differentiated into TGF-β-enriched tissues. Furthermore, CXCL12<sup>+</sup> TAMs recruited PD-L1<sup>+</sup> Bregs via the CXCL12/CXCR4 axis, and CXCR4 expression was significantly positively correlated to PD-L1 expression in PD-L1<sup>+</sup> Bregs. At last, we confirmed the communications among CAFs, Macrophages and B cells and their tumor-promoting effects by using an orthotopic mouse model of HCC. Immunosuppressive HCC TME involving cell-to-cell communications comprised MIF-secreting CAFs, CXCL12-secreting TAMs, and PD-L1-producing Bregs, and their regulation could be promising therapeutic targets in future immunotherapy for human HCC.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-06-26T03:12:33.816Z","creation":"2026-06-26T03:07:10.62Z"},"accession":"S-EPMC10915331","cross_references":{"pubmed":["38455420"],"doi":["10.62347/ziax8828"]}}