Discovery and validation of proliferative exhausted T cells as a favorable prognostic biomarker in esophageal squamous cell carcinoma.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with limited therapies and poor prognosis. While exhausted T cell (Tex) heterogeneity under chronic antigen stimulation is recognized, the role of Tex subsets in shaping the tumor microenvironment (TME) and influencing ESCC outcomes remains unclear. We integrated single-cell RNA sequencing, TCR sequencing, microarray, and bulk RNA sequencing to dissect Tex cells. We identified a novel proliferative Tex (prolif Tex) subset across discovery and validation cohorts, with high infiltration correlating significantly with an improved patient survival. Pseudotime trajectories suggested prolif Tex originated from Tex cells, while TCR sequencing revealed clonal expansion and shared receptor repertoires between Tex and prolif Tex.

SUBMITTER: Li G 

PROVIDER: S-EPMC12644482 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature