{
  "abstract": "Background Histopathological growth patterns (HGPs), specifically desmoplastic (dHGP) and replacement (rHGP), serve as critical prognostic determinants in colorectal cancer liver metastases (CRLM). However, the underlying mechanisms governing these distinct clinical phenotypes remain poorly understood. Here, we aimed to delineate the spatial landscape and identify targetable molecular drivers of HGP formation in CRLM.Methods We performed single-cell RNA sequencing on primary colorectal cancer, liver metastasis and adjacent liver tissues from 17 CRLM patients, integrated by spatial transcriptomics of 8 paired liver metastasis samples containing both dHGP and rHGP regions. The identified CCL20-CCR6 axis was functionally validated using in vitro assays and in vivo CRLM mouse models with a CCR6 inhibitor.Results Clinically, dHGP liver metastases were associated with improved prognosis and exhibited significantly higher prevalence of tertiary lymphoid structures (TLS) compared to rHGP lesions. Spatial and single-cell profiling revealed that the dHGP tumor microenvironment is characterized by an enrichment of CXCL13 + follicular helper T cells and CCL19+ fibroblastic reticular cells at the invasive margin, which collaboratively promoted TLS formation and maturation. In contrast, rHGP liver metastases are dominated by a CCL20-rich immunosuppressive niche. Mechanistically, motility-associated tumor cell subsets and CCL20+ macrophages at the invasive margin selectively recruited regulatory T cells via the CCL20-CCR6 axis. This recruitment subsequently suppressed IgG+ plasma cell differentiation and impaired TLS formation, thereby promoting an immune-excluded phenotype. Notably, blocking the CCL20-CCR6 axis with a CCR6 inhibitor in liver metastases mouse models effectively restored TLS formation and suppressed CRLM progression.Conclusions Our findings identify the CCL20-CCR6 axis as a crucial immune regulator in CRLM. Targeting this axis represents a promising strategy to convert immune-excluded rHGP liver metastases into an immune-active state, providing a novel therapeutic avenue for CRLM management.",
  "authors": [
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Yuting Hong"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Xiaoxue Ren"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Yifan Zhang"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Zhihang Chen"
    }
  ],
  "title": "IDDF2026-ABS-0075 Tumor–macrophage CCL20 impairs tertiary lymphoid structure formation in colorectal cancer liver metastases via recruitment of CCR6+ regulatory T cells",
  "uid": "116c6a7a-4760-5488-82c0-002e977b4a3c"
}