Oral squamous cell carcinoma (OSCC) is a major malignancy in South Asia, driven by betel nut/tobacco use, with 5-year survival near 50-60% and frequent recurrences reflecting its aggressive biology. Although tissue resident memory (TRM) T cells mediate innate immunity, their spatial organization and associated regulatory role of cytokine, interleukin-15 (IL-15) in the OSCC tissues and their microenvironment remain unclear.This study aimed to map CD4⁺ and CD8⁺ T lymphocytes, and TRM markers (CD103, CD49a, CD69) across tumor and stromal compartments, to assess the regulatory role of IL-15 and CD103 associated epithelial E-cadherin interactions and build a multivariate prognostic model.Method Eighty OSCC cases confirmed by histopathological examination. Formalin-fixed, paraffin-embedded tumor tissues (~ 1 g) from surgical resections underwent immunohistochemistry. Whole-slide digital imaging (×40) quantified CD4⁺ and CD8⁺ T lymphocytes, and TRM markers across tumor and stromal fields. Staining intensity and percent scores were generated as a composite score (0-3). Inter-observer reliability (Kendall's τ ≥ 0.7) was verified. Associations were tested using χ²/Fisher's exact, while survival was analyzed by Kaplan-Meier and Cox regression (HR, 95% CI).Results Immune and epithelial marker expression varied significantly across tumor and stromal compartments (p < 0.001). Advanced tumor stage predicted poor survival (p = 0.044). Retained E-cadherin correlated with improved survival (p = 0.027), while CD49a expression was associated with adverse outcomes (p = 0.006). Multivariate Cox regression identified CD103 (Adj.HR 2.02, 95% CI 1.03-3.96) and E-cadherin (Adj.HR 3.01, 95% CI 1.25-7.23) as independent adverse predictors, whereas stromal CD8 (HR 0.35, 95% CI 0.14-0.99) and CD49a (HR 0.37, 95% CI 0.14-0.98) were protective. High IL-15 expression showed a positive association with CD103⁺ TRM T cell infiltration, particularly within the stromal compartment, although the association did not reach statistical significance (p = 0.076).Conclusion The spatial interplay among IL-15 expression, CD103⁺ immune infiltration, and the localization of TRM-associated markers suggests the presence of an integrated immune-epithelial axis associated with OSCC progression and may provide prognostic and therapeutic insights.

Background 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. Methods 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. Results 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). Conclusions 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.