{
  "abstract": "Background Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy with rising global incidence. Neural invasion (NI) occurs in up to 70% of ICC patients and is recognized as an independent predictor of poor prognosis. However, the cellular architecture and molecular interactions within and surrounding tumor-associated nerves remain poorly understood. Herein, we aimed to systematically dissect the tumor-neural microenvironment and investigate the crosstalk between malignant cells, Schwann cells, immune cells, and cancer-associated fibroblasts (CAFs) in ICC.Methods Tumor tissues and clinical data from ICC patients were analyzed using single-cell RNA sequencing (scRNA-seq), spatial-enhanced-resolution-omics-sequencing (Stereo-seq) and multiplex immunohistochemistry to characterize cellular phenotypes and spatial organization. The biological roles and mechanisms of Schwann cells and CAFs in ICC were determined using the in vitro co-culture system and in vivo mouse models.Results Clinically, neural invasion was significantly associated with poor survival in ICC patients. Integrated scRNA-seq and Stereo-seq analyses revealed distinct cellular compositions and spatial architectures associated with NI status. Basal-like malignant subpopulations and inflammatory CAFs (iCAFs) were preferentially enriched in the perineural niche of NI-positive tumors. Basal-like tumor cells exhibited activation of nerve-related signaling programs, including axon guidance and nerve development. Among stromal populations, iCAFs displayed the highest neural interaction potential and recruited Schwann cells via the IGF1-IGF1R axis, thereby promoting Schwann cell proliferation and invasion. Notably, Schwann cells in the NI microenvironment engaged extensive interactions with CD8+GZMK+ effector memory T cells, driving a stressed and exhausted state accompanied by impaired cytotoxic activity. This Schwann cell-mediated T cell dysfunction contributed to an immunosuppressive niche that facilitated tumor progression. Importantly, pharmacological inhibition of IGF1R significantly reversed the immunosuppressive microenvironment and suppressed tumor growth in the orthotopic model.Conclusions Basal-like malignant cells orchestrate CAFs and Schwann cells reprogramming to establish an immunosuppressive tumor-neural niche that promotes ICC progression. Targeting cancer-immune-neural interactions represents a promising therapeutic strategy for ICC.",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China"
      ],
      "name": "Ye Yang"
    },
    {
      "affiliations": [
        "Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China"
      ],
      "name": "Yuting Hong"
    },
    {
      "affiliations": [
        "Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China"
      ],
      "name": "Shijia Liu"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China"
      ],
      "name": "Sui Peng"
    },
    {
      "affiliations": [
        "Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China"
      ],
      "name": "Zhihang Chen"
    },
    {
      "affiliations": [
        "Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China"
      ],
      "name": "Xiaoxue Ren"
    }
  ],
  "title": "IDDF2026-ABS-0187 Crosstalk between schwann cells and iCAF Shapes an immunosuppressive microenvironment in intrahepatic cholangiocarcinoma",
  "uid": "deb5a05b-b022-5a7d-845e-25e7d9348c06"
}