Collectively, our integrative analysis of public scRNA‐seq data, GEPIA database, and CRC TNM staging cohorts revealed that tumour cells with high stemness‐related gene expression (RPS7, RPL8 and RPL30) resist TNF‐mediated immunoregulation, while dynamic changes in TNFRSF18 and CXCL13 expression in CD8+ T cells provide promising biomarkers for early CRC screening and monitoring of T cell exhaustion. Here, TNF is linked to neoplasm.