AUTHOR=Hu Jiaqi , Han Chongyin , Zhong Jiayuan , Liu Huisheng , Liu Rui , Luo Wei , Chen Pei , Ling Fei 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.691142

DOI=10.3389/fimmu.2021.691142

ISSN=1664-3224

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