Abstract 6157: Single-cell characterization of tumor niches driving liver metastasis in colorectal cancer

Abstract Metastasis has been linked to the tumor microenvironment, but the cellular interaction networks that organize metastatic niches in microsatellite-stable colorectal cancer are not fully characterized. We performed single-cell RNA sequencing of colon normal tissue, primary colorectal tumors, liver metastases, and matched liver normal tissue to define microenvironmental remodeling with a focus on T-cell and fibroblast compartments. Tumor-associated fibroblasts showed broad upregulation of collagen genes, enrichment of apical junction and surface-related pathways, increased communication among fibroblast subsets, and the emergence of metastasis-associated fibroblast populations. In parallel, liver metastases exhibited depletion of CD8+ T cells and NK cells compared with liver normal tissue, accumulation of regulatory T cells and CD8+ exhausted T cells and strengthened fibroblast-CD8+ T-cell interactions. Ligand-receptor analysis revealed CLEC signaling between fibroblasts and T cells across multiple conditions, with selectively enhanced CLEC-mediated interactions in liver metastases compared with liver normal tissue. Galectin-mediated communication was restricted to tumor settings and, while broadly distributed across fibroblast clusters in primary tumors, became selectively intensified within a specific fibroblast subset in liver metastases. Fibroblasts in liver metastases also preferentially engaged CD8+ exhausted T cells through NRXN signaling. Together, these data delineate fibroblast-centered, site-specific signaling circuits that shape immune composition and function during metastatic progression and nominate fibroblast-T-cell communication hubs as candidate targets for modulating the tumor niche in microsatellite-stable colorectal cancer. Citation Format: Jinho Jang, Yoojeong Seo, Kyung Pil Ko, Jie Zhang, Sohee Jun, Jae-Il Park. Single-cell characterization of tumor niches driving liver metastasis in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6157.