Construction of a Novel T Cell Subtype with Immunotherapeutic Value in Bladder Cancer and a Neural Network-Based Prognostic Model

Bladder cancer (BLCA) remains a significant global health challenge, characterized by high heterogeneity and suboptimal responses to existing immunotherapies. This study identifies TNFRSF4/CD4+ T cells as a novel immune cell subtype with crucial prognostic and therapeutic relevance in BLCA. Leveraging single-cell RNA sequencing and bulk transcriptome data from TCGA-BLCA and GEO databases, we conducted multi-omics analyses to elucidate the immune landscape and its implications for clinical outcomes. Our findings reveal that higher levels of TNFRSF4/CD4+ T cells are associated with improved patient survival and robust immune activity, emphasizing their potential as biomarkers and therapeutic targets. Gene expression and pathway enrichment analyses highlight their involvement in immune-regulatory mechanisms, including the TCR signaling pathway and TNF family signaling. Additionally, we identified 11 core genes associated with TNFRSF4/CD4+ T cells, such as SEPTIN1 and FCMR, which significantly impact prognosis and immune function. Multiplex immunofluorescence demonstrated a strong positive correlation between the prognosis of bladder cancer patients and the expression of SEPTIN1 and FCMR within TNFRSF4/CD4+ T cells. These genes served as the foundation for constructing a neural network-based prognostic model, which demonstrated high predictive accuracy and stratified patients into distinct risk categories. This study underscores the critical role of TNFRSF4/CD4+ T cells in BLCA immunity and highlights their potential in advancing personalized treatment strategies, offering novel insights into improving immunotherapy efficacy in bladder cancer.