In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-8-9)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.691142
DOI:
10.3389/fimmu.2021.691142.s001
DOI:
10.3389/fimmu.2021.691142.s002
DOI:
10.3389/fimmu.2021.691142.s003
DOI:
10.3389/fimmu.2021.691142.s004
DOI:
10.3389/fimmu.2021.691142.s005
DOI:
10.3389/fimmu.2021.691142.s006
DOI:
10.3389/fimmu.2021.691142.s007
Sprache:
Unbekannt
Verlag:
Frontiers Media SA
Publikationsdatum:
2021
ZDB Id:
2606827-8
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