祖细胞耗竭 T 细胞作为食管鳞状细胞癌的预后指标：揭示其对肿瘤免疫的关键贡献

Despite notable advances with immune checkpoint inhibitors (ICIs) in esophageal squamous cell carcinoma (ESCC), their clinical efficacy remains limited, largely due to CD8⁺T cell exhaustion. Among these, progenitor exhausted T cells (T pex ) represent a key subset with stem cell-like features that sustain durable anti-tumor immunity.

We applied multi-color immunohistochemistry (mIHC) to determine the spatial distribution and clinical significance of T pex cells within the tumor microenvironment (TME) of ESCC. Publicly available single-cell RNA sequencing (scRNA-seq) datasets were further analyzed to characterize T pex cell phenotypes, differentiation trajectories, and intercellular communication networks.

T pex cells constituted a distinct subset of infiltrating CD8⁺T cells and represented a transitional stage of the exhaustion continuum. A higher degree of T pex infiltration was significantly associated with improved overall survival in ESCC patients. Moreover, scRNA-seq data from patients treated with PD-1 blockade revealed that responders harbored markedly enriched T pex populations compared with non-responders.

Our findings identify T pex cells as a critical prognostic and immunologically active CD8⁺T cell subset in ESCC. Their abundance and functional engagement are closely associated with favorable clinical outcomes and response to PD-1 blockade. Furthermore, their stem cell-like properties may be pivotal in shaping durable anti-tumor immunity and could provide novel therapeutic targets to enhance the efficacy of PD-1-based immunotherapy.