Spatial profiling of tissue-resident memory T cells reveals stromal IL-15 niches and a paradoxical CD103⁺ phenotype predicting survival in oral squamous cell carcinoma.

Authors

Anwar Ali, Muhammad Furqan Bari, Saba Arshad, Mohsin Wahid, Jawad Safdar, Khadija Anwar, Waqas Ahmed Farooqui

Published in

BMC cancer. Jul 03, 2026. Epub Jul 03, 2026.

Abstract

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.

PMID:
42399859
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.

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