IL7 as a Risk Factor for Prostate Cancer: Implications for T Cell Apoptosis and Infiltration in the Tumor Microenvironment.

Abstract

Background: Prostate cancer's complex interplay with the immune microenvironment prompted an investigation into immune-related pathogenic mechanisms and potential therapeutic targets.

Methods: Within the GSE176031 data set, Seurat meticulously dissected single-cell profiles from radical prostatectomy patients. Leveraging CellMarker and SingleR cell identities were precisely annotated. Then, monocle traced pseudotime trajectories, illuminating cellular paths, complemented by CellChat's insights into intricate intercellular communications. Furthermore, mendelian randomization (MR) robustly substantiated causal associations within prostate cancer contexts.

Results: Employing single-cell analysis on intraoperative tumor and normal tissue, we identified 15 distinct cell types, notably observing a significant T cell reduction in tumor samples. Intercellular communication analysis revealed multiple pathways between epithelial cells and T cells, highlighting interleukin (IL)-IL7R-IL2RG interactions. IL7R, crucial in T cell apoptosis, showed differential expression across T cell development stages. Patients with IL7 amplification had poorer outcomes (p < 0.05), supported by MR in two cohorts (ieu-b-4809 cohort: odds ratio [OR] = 1.005, p = 0.002, 95% confidence interval [CI] [1.002-1.008]; ebi-a-GCST90018905: OR = 1.063, p = 0.032, 95% CI [1.005-1.125]), confirming IL7 as a prostate cancer risk factor.

Conclusions: These findings suggest T cell depletion via IL7-IL7R signaling may drive prostate cancer progression, offering novel therapeutic insights.