The compartment specific stromal and tumor expressions of TIGIT, CD39, TNF-α, and IFN-γ in oral squamous cell carcinoma

The spatial organization of immune checkpoint, metabolic, and cytokine effector markers within the oral squamous cell carcinoma (OSCC) tumor microenvironment remains uncharacterized. TIGIT, CD39, TNF-α, and IFN-γ were selected to capture complementary arms of immune regulation, checkpoint inhibition, metabolic suppression, and cytokine effector function, whose spatial interplay may influence clinical outcomes. This study investigated their compartment-specific expression and prognostic significance in OSCC tumor tissues and peritumoral stroma. Eighty OSCC cases were evaluated. Immunohistochemical expressions of TIGIT, CD39, TNF-α, and IFN-γ markers were assessed separately in tumor compartment and peritumoral stroma. Associations with overall survival were examined using chi-square or Fisher’s exact tests and TNM stage-adjusted Cox regression. CD39, TIGIT, and TNF-α showed predominantly intermediate-to-high expression in peritumoral stroma, with descriptively different patterns across compartments. TIGIT positivity was associated with lower mortality hazard in both compartments (tumor: HR = 0.29; stroma: HR = 0.21). IFN-γ positivity was associated with lower mortality hazard in stroma (HR = 0.49), while no significant association was observed in tumor (HR = 0.85). TIGIT and IFN-γ are associated with improved survival in OSCC, with TIGIT showing consistent associations across compartments and IFN-γ demonstrating stromal specificity. These findings suggest that tissue compartment may influence the prognostic relevance of immune biomarkers and may support future compartment-aware approaches to risk stratification and immune profiling. Validation in larger, independent cohorts is warranted.