Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36221095", "kind": "science-record", "revision": 3, "content_hash": "sha256:b88032033164d28774a90709af24b0194adb7db09d0ac4d76b1b36ac2d276711", "created_at": "2026-11-01T18:15:34Z", "updated_at": "2026-11-01T21:29:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma.", "doi": "10.1186/s12967-022-03675-2", "pmid": "36221095", "authors": ["Zhuomao Mo", "Daiyuan Liu", "Yihan Chen", "Jin Luo", "Wenjing Li", "Jiahui Liu", "Ling Yu", "Bijun Huang", "Shijun Zhang"], "journal": "Journal of translational medicine", "year": 2022, "abstract": "BACKGROUND: Liver carcinoma generally presents as an immunosuppressive microenvironment that promotes tumor evasion. The intercellular crosstalk of immune cells significantly influences the construction of an immunosuppressive microenvironment. This study aimed to investigate the important interactions between immune cells and their targeting drugs in liver carcinoma, by using single-cell and bulk transcriptomic data.\nMETHODS: Single-cell and bulk transcriptomic data were retrieved from Gene Expression Omnibus (GSE159977, GSE136103, and GSE125449) and The Cancer Genome Atlas (TGCA-LIHC), respectively. Quality control, dimension reduction, clustering, and annotation were performed according to the Scanpy workflow based on Python. Cell-cell interactions were explored using the CellPhone database and CellChat. Trajectory analysis was executed using a partition-based graph abstraction method. The transcriptomic factors (TFs) were predicted using single-cell regulatory network inference and clustering (SCENIC). The target genes from TFs were used to establish a related score based on the TCGA cohort; this score was subsequently validated by survival, gene set enrichment, and immune cell infiltration analyses. Drug prediction was performed based on the Cancer Therapeutics Response Portal and PRISM Repurposing datasets.\nRESULTS: Thirty-one patients at four different states, including health, hepatitis, cirrhosis, and cancer, were enrolled in this study. After dimension reduction and clustering, twenty-two clusters were identified. Cell-cell interaction analyses indicated that macrophage-naive CD4 + T cell interaction significantly affect cancerous state. In brief, macrophages interact with naive CD4 + T cells via different pathways in different states. The results of SCENIC indicated that macrophages present in cancer cells were similar to those present during cirrhosis. A macrophage-naive CD4 + T cell (MNT) score was generated by the SCENIC-derived target genes. Based on the MNT score, five relevant drugs (inhibitor of polo-like kinase 1, inhibitor of kinesin family member 11, dabrafenib, ispinesib, and epothilone-b) were predicted.\nCONCLUSIONS: This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma. Tumor-associated macrophages may be derived from cirrhosis and can initiate liver carcinoma. Predictive drugs that target the macrophage-naive CD4 + T cell interaction may help to improve the immunosuppressive microenvironment and prevent immune evasion. The relevant mechanisms need to be further validated in experiments and cohort studies.", "claims": [{"id": "claim-method", "statement": "Cell–cell interactions were explored using the CellPhone database and CellChat. The enriched ligand-receptor interactions were calculated based on a permutation test. p < 0.01 were considered significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36221095", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Cell–cell interactions were explored using the CellPhone database and CellChat."}, {"asset": "source:pmid:36221095", "locator": "sections[7] \"Cell–cell interaction analyses\" paragraph 2", "quote": "The enriched ligand-receptor interactions were calculated based on a permutation test. p < 0.01 were considered significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during the current study are available in the TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ICGC database (https://dcc.icgc.org/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36221095", "locator": "sections[35] \"notes\" paragraph 1", "quote": "The datasets generated during the current study are available in the TCGA database (https://portal.gdc.cancer.gov/), GEO database (https://www.ncbi.nlm.nih.gov/geo/) and ICGC database (https://dcc.icgc.org/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36221095", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study reveals the crucial role of macrophage-naive CD4 + T cell interaction in the immunosuppressive microenvironment of liver carcinoma.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36221095"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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