Our results further elucidated the specific mechanism of this phenomenon, and scRNA-seq analysis found that CD4-CXCL13Tfh induced an increase in CD8-PDCD1 exhausted T cells in CRC TME through elevating expression of COX17, while COX17 also likely induced CD4-CCR7-TCF7 Naïve T cells to become immunosuppressive CD4-CXCL13 T cells and further worsen TME. Here, COX17 is linked to colorectal carcinoma.