Crosstalk among T cells, epithelial cells, and fibroblasts identifies a prognostic signature in oral squamous cell carcinoma

Abstract Objectives This study aimed to analyze the crosstalk network among T cells, epithelial cells, and fibroblasts in the tumor microenvironment of oral squamous cell carcinoma (OSCC) and to determine their prognostic values. Materials and Methods Single‐cell subpopulation identification and communication analysis identified crosstalk markers. The least absolute shrinkage and selection operator Cox analysis identified key prognostic features by integrating the bulk transcriptome and clinical parameters. Functional analysis and immune infiltration were explored to determine possible mechanisms. Results Interactions between epithelial cells and fibroblasts primarily involve MIF, MK, PTN, IGF, EGF, and PERIOSTIN, whereas T cells interact with epithelial cells and fibroblasts through MIF, CXCL, PAR, IFN, and EGF signals. We constructed a novel prognostic feature comprising 13 crosstalk genes: HBEGF, FGF7, GRN, ITGB5, CXCR6, ERBB2, AREG, F2RL2, NAMPT, KLK12, HMGB2, TUBA1B, and KLRD1. Patients were stratified based on the RiskScore. Functional analysis revealed that the high‐risk group was enriched in immunosuppressive pathways ( p < 0.001). Immune checkpoints including PD‐1, PD‐L1, and CTLA4 were more highly expressed in the high‐risk group ( p < 0.05). Conclusions The crosstalk network among T cells, epithelial cells, and fibroblasts is complex and may have implications for prognosis and clinical treatments of OSCC patients.