We are analyzing https://link.springer.com/article/10.1186/s12967-022-03675-2.

Title:
Single-cell transcriptomics reveals the role of Macrophage-Naïve CD4 + T cell interaction in the immunosuppressive microenvironment of primary liver carcinoma | Journal of Translational Medicine
Description:
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. Methods 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. Results 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. Conclusions 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. Graphical Abstract
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Keywords {🔍}

cells, cell, cancer, pubmed, cirrhosis, macrophages, article, liver, data, genes, fig, naïve, interaction, analysis, hepatitis, macrophage, google, scholar, states, treg, carcinoma, score, cas, immune, transcriptomic, singlecell, interactions, signaling, based, macrophagenaïve, study, results, central, gene, employed, microenvironment, immunosuppressive, performed, additional, health, file, gse, network, analyses, drug, pathway, ccl, state, mnt, found,

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hg19-tss-centered-10 kb-7species multi-subunit ligand–receptor complexes multi-sector single-cell atlas single-cell rna-seq sun yat-sen university mif-related ligand-receptor interactions regulon-activity-based hierarchical clustering hg19-500 bp-upstream-7species partition-based graph abstraction full size image single-cell transcriptomics reveals multimeric receptor-ligand complexes library-size correction method tp53-mutant hepatocellular carcinoma single-cell sequencing data single-cell transcriptomic data related ligand-receptor interactions related ligand-receptor interaction comprehensive single-cell atlas article download pdf infer cell–cell interactions cd1c + _a dendritic cells cd1c + _b dendritic cells cd141-cd1c-dendritic cells stage iii/stage iv myeloid-derived suppressor cells enriched ligand-receptor interactions low-score groups based inferring cell–cell communication leiden graph-clustering method inflammation-induced hepatocellular carcinoma cell-type-specific markers cd141 + clec9a + dendritic cells cancer microenvironment cd4-positive full access lasso regression model cell–cell interaction analyses cell–cell interaction analysis related subjects single-cell sequencing remains poorly understood xcl1 + natural killer cells gnly + natural killer cells privacy choices/manage cookies gene regulatory network gene set enrichment hepatic stellate cell advanced hepatocellular carcinoma finn rs single cell transcriptomic

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WebPage:
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         description: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. 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. 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. 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.
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         Macrophage
         Naïve CD4 + T cell
         Tumor microenvironment
         Immunosuppression
         Biomedicine
         general
         Medicine/Public Health
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      name:Center for Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, China
      name:Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
      name:Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China
      name:Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
      name:Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
      name:Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
      name:Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
      name:Guangdong Province Hospital of Chinese Medicine, AMI Key Laboratory of Chinese Medicine in Guangzhou, Guangzhou, China
      name:Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
      name:Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China

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