Multi‐omics profiling identifies TNFRSF18 as a novel marker of exhausted CD8⁺ T cells and reveals tumour‐immune dynamics in colorectal cancer

作者：Tengfei Jia, Yingxi Guo, Xin meng Cheng, Zeyang Zhou, Xiaojiang Xu, Hebin Liu, Xiaodong Yang · 发表于：Clinical and Translational Medicine · 年份：2025 · DOI：10.1002/ctm2.70425 · 被引用次数：9 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、T-cell and B-cell Immunology

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignant tumours of the digestive system globally and is associated with unfavourable survival outcomes. The exhaustion of CD8⁺ T cells serves a crucial role in facilitating tumour immune escape. Yet, the dynamic evolution of CD8⁺ T cell exhaustion and its impact on clinical prognosis across TNM (tumour-node-metastasis) stages in CRC remains incompletely characterized. METHODS: Tumour and adjacent tissues (20 samples total) from 6 CRC patients spanning diverse TNM stages were analyzed using integrated single-cell transcriptomic profiling (scRNA-seq), single-cell T cell receptor/B cell receptor sequencing (scVDJ-seq), and spatial transcriptomics. T cell exhaustion markers, immune clonality, gene expression profiles, and the spatial distribution of both tumour cells and immune cells were systematically profiled. Functional enrichment and intercellular communication analyses were conducted. Key findings were validated using immunofluorescence and public datasets. RESULTS: Our results illustrate how advancing TNM stages in CRC shape CD8⁺ T cell exhaustion through divergent TNFRSF18/CXCL13 dynamics and ribosomal stemness. TNFRSF18 expression was notably higher in T cells infiltrating tumour tissues relative to their counterparts in adjacent non-tumorous areas, with high-expressing CD8⁺ T cells exhibiting marked exhaustion features. During CRC progression, TNM-stage-driven remodelling of the tumour microenvironment...