Single-cell and spatial transcriptome profiling identifies cellular heterogeneity and immunosuppressive tumor microenvironment in inflammatory breast cancer

作者：Xueni Sun, Jing Xia, Haiyang Jiang, Ting Duan, Chunli Zhang, Qinyi Li, Zuyi Yang, Ruonan Zhang, Xia Ding, Xidong Gu, Xiaohong Xie, Tian Xie, Xinbing Sui · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.05.061 · 被引用次数：7 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

INTRODUCTION: Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer associated with a poor prognosis. A better understanding of IBC's pathological and molecular basis is crucial for developing precision medicine strategies. OBJECTIVE: This study aimed to profile IBC at both the single-cell and spatial levels to examine immune cell populations, signaling pathways, and identify potential therapeutic targets for treating IBC. METHODS: Single-cell RNA sequencing (scRNA-seq) was employed to identify immune-related differences between IBC and non-IBC samples. qRT-PCR and fluorescence staining were utilized to validate the findings from scRNA-seq, while spatial analysis using the NanoString GeoMx Digital Spatial Profiler was conducted to evaluate immune cell infiltration. Tumor-immune cell co-culture assays were conducted to assess the cytotoxic role of CXCL13. In vivo studies were performed to assess the effect of CXCL13 on the efficacy of immunotherapy. Furthermore, a screening of natural products was performed to identify potential immunomodulatory agents for the treatment of IBC. RESULTS: scRNA-seq revealed a significant reduction in CXCL13 expression in T cells within the IBC tumor microenvironment, a finding that correlated with poorer patient outcomes. Additionally, immune-related gene sets were notably downregulated, and cell-cell interactions were diminished, indicating a state of immune suppression within IBC. Spatial analysis further demonstrate...