Work

The Proximity of PD-1−CD103+ Tissue-Resident CD8+ T Cells to Tumor Cells Is Correlated with Improved Clinical Outcomes in Patients with Cholangiocarcinoma

Year: 2026

Type: article

Abstract: Background/Objectives: Cholangiocarcinoma (CCA) is characterized by a heterogeneous immune microenvironment, where the prognostic significance of CD8+ tissue-resident memory T (TRM) cell activation and spatial positioning remains to be fully elucidated. This study investigated how the activation phenotypes and their spatial distribution relative to tumor cells influence anti-tumor immunosurveillance and predict clinical outcomes in CCA. Methods: Multiplex immunohistochemistry (mIHC) and single-cell RNA sequencing (scRNA-seq) were employed to characterize naïve (PD-1−CD103+CD8+) and exhausted (PD-1+CD103+CD8+) subsets. G-cross function analysis was utilized to quantify the spatial proximity between these specific TRM subsets and tumor cells, correlating the spatial interaction with patient overall survival. Results: scRNA-seq profiling revealed that PD-1−CD103+CD8+ TRM cells were enriched in genes associated with lymphocyte activation and cytotoxicity, while PD-1+CD103+CD8+ TRM cells exhibited an exhaustion signature. Spatially, PD-1−CD103+CD8+ TRM cells exhibited increased interactions with tumor cells, whereas PD-1+CD103+CD8+ TRM cells showed reduced engagement. Therefore, the close proximity of PD-1−CD103+CD8+ TRM cells to tumor cells was identified as a significant predictor of favorable clinical outcomes. Conclusions: The activation state of CD8+ TRM cells combined with their spatial localization constitutes a critical prognostic factor in CCA. Effective anti-tumor immunosurveillance relies on the direct engagement of naïve TRM cells with tumor cells. These findings highlight the potential of PD-1-targeted immunotherapies to remodel the spatial proximity of the tumor microenvironment, potentially promoting the redistribution of effector cells into tumor-proximal regions.

Source: Cancers

DOI: 10.3390/cancers18040680