Scholarlink

<p>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.</p><p>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.</p><p><b>Method </b>Eighty OSCC cases confirmed by histopathological examination. Formalin-fixed, paraffin-embedded tumor tissues (~ 1&#xa0;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).</p><p><b>Results </b>Immune and epithelial marker expression varied significantly across tumor and stromal compartments (<i>p</i> &lt; 0.001). Advanced tumor stage predicted poor survival (<i>p</i> = 0.044). Retained E-cadherin correlated with improved survival (<i>p</i> = 0.027), while CD49a expression was associated with adverse outcomes (<i>p</i> = 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<sup>+</sup> TRM T cell infiltration, particularly within the stromal compartment, although the association did not reach statistical significance (<i>p</i> = 0.076).</p><p><b>Conclusion </b>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月3日

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

摘要

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.