Dataset Information

Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer.

ABSTRACT: Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4⁺ and dysfunctional CD8⁺ T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD4⁺ T cells, while FCN3⁺ macrophages, type 1 conventional dendritic cells (cDC1) and LAMP3⁺ DC regulated T cell functions, probably via antigen processing and presentation. Major histocompatibility complex expression in FCN3⁺ macrophage, cDC1 and LAMP3⁺ DC was reduced in LM compared to those in normal tissues and primary BC. Malfunctioned antigen presentation in these cells is linked to a worse prognosis in invasive BC and hepatocellular carcinoma. Our results provide valuable insights into the role of tumor infiltrating T cells in LM.

SUBMITTER: Wang X

PROVIDER: S-EPMC10839686 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer.

Wang Xiaoshuang X Zhou Yan Y Wu Zhongen Z Xie Cao C Xu Weiqi W Zhou Qingtong Q Yang Dehua D Zhu Di D Wang Ming-Wei MW Wang Lu L

iScience 20240112 2

Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4<sup>+</sup> and dysfunctional CD8<sup>+</sup> T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD ...[more]

PMID: 38318373

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Project description:BackgroundLiver 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.MethodsSingle-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.ResultsThirty-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.ConclusionsThis 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.

Dataset Information

Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer.

Publications

Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer.

Similar Datasets

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