Image_2_Dynamic Network Biomarker of Pre-Exhausted CD8+ T Cells Contributed to T Cell Exhaustion in Colorectal Cancer.tif (3.36 MB)
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posted on 09.08.2021, 04:44 authored by Jiaqi Hu, Chongyin Han, Jiayuan Zhong, Huisheng Liu, Rui Liu, Wei Luo, Pei Chen, Fei Ling

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, CCT6A identified by DNB was a biomarker for pre-exhausted T-cell subpopulation in CRC. Besides, TUBA1B expression was triggered by CCT6A as DNB core genes contributing to CD8+ T cell exhaustion, indicating that core genes serve as biomarkers in pre-exhausted T cells. Remarkably, both TUBA1B and CCT6A expressions were significantly associated with the overall survival of COAD patients in the TCGA database (p = 0.0082 and p = 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.

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