Dynamic Network Biomarker of Pre-Exhausted CD8 T Cells Contributed to T Cell Exhaustion in Colorectal Cancer.

Immunotherapy has achieved positive clinical responses in various cancers. However, in advanced colorectal cancer (CRC), immunotherapy is challenging because of the deterioration of T-cell exhaustion, the mechanism of which is still unclear. In this study, we depicted CD8 T-cell developmental trajectories and characterized the pre-exhausted T cells isolated from CRC patients in the scRNA-seq data set using a dynamic network biomarker (DNB). Moreover, identified by DNB was a biomarker for pre-exhausted T-cell subpopulation in CRC. Besides, expression was triggered by as DNB core genes contributing to CD8 T cell exhaustion, indicating that core genes serve as biomarkers in pre-exhausted T cells. Remarkably, both and expressions were significantly associated with the overall survival of COAD patients in the TCGA database ( = 0.0082 and = 0.026, respectively). We also observed that cellular communication between terminally differentiated exhausted T cells and pre-exhausted T cells contributes to exhaustion. These findings provide new insights into the mechanism of T-cell exhaustion and provide clue for targeted immunotherapy in CRC.