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Objective <p>In pancreatic ductal adenocarcinoma (PDAC), immune and stromal components of the tumor microenvironment critically influence disease progression and survival. Although FoxP3 expression has been linked to prognosis, the clinical relevance of its spatial distribution remains unclear. This study aimed to evaluate the prognostic significance of FoxP3-positive lymphocytes in intratumoral (IT), peritumoral (PT), and tumor-associated stromal (T) compartments.</p> Materials and methods <p>Ninety-eight patients with PDAC who underwent surgical resection between 2015 and 2021 were retrospectively analyzed. FoxP3 expression was assessed immunohistochemically in IT, PT, and T compartments and categorized as low or high based on H-scores. Associations with clinicopathological variables, overall survival (OS), and disease-free survival (DFS) were analyzed using Kaplan–Meier and Cox proportional hazards models. Subgroup analyses were performed according to recurrence status and receipt of adjuvant chemotherapy.</p> Results <p>High FoxP3 expression in IT, PT, and T compartments was significantly associated with shorter OS. Although FoxP3 expression showed significant associations with DFS in Kaplan–Meier analyses, it did not retain independent significance in multivariate models. Tumor-associated stromal FoxP3 expression correlated with increased stromal response and advanced nodal stage, whereas high PT-FoxP3 expression was associated with positive surgical margins. In patients receiving adjuvant chemotherapy, Kaplan–Meier analyses showed no clear survival separation; however, compartment-specific prognostic effects of FoxP3 were preserved in multivariate analyses.</p> Conclusion <p>FoxP3-positive lymphocyte infiltration represents a clinically relevant prognostic biomarker in PDAC, with its impact on survival strongly dependent on spatial localization within the tumor microenvironment. Compartment-based evaluation of FoxP3 may improve risk stratification and provide a biologically meaningful framework for future immunologically informed therapeutic strategies in PDAC.</p>

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Spatially resolved FoxP3 positive lymphocyte infiltration within the tumor microenvironment predicts survival in resected pancreatic ductal adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月26日

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  • Hilal Kandemir,
  • Dudu Solakoglu Kahraman,
  • Safiye Aktas,
  • Olcun Umit Unal,
  • Serhat Cagiral

摘要

Objective

In pancreatic ductal adenocarcinoma (PDAC), immune and stromal components of the tumor microenvironment critically influence disease progression and survival. Although FoxP3 expression has been linked to prognosis, the clinical relevance of its spatial distribution remains unclear. This study aimed to evaluate the prognostic significance of FoxP3-positive lymphocytes in intratumoral (IT), peritumoral (PT), and tumor-associated stromal (T) compartments.

Materials and methods

Ninety-eight patients with PDAC who underwent surgical resection between 2015 and 2021 were retrospectively analyzed. FoxP3 expression was assessed immunohistochemically in IT, PT, and T compartments and categorized as low or high based on H-scores. Associations with clinicopathological variables, overall survival (OS), and disease-free survival (DFS) were analyzed using Kaplan–Meier and Cox proportional hazards models. Subgroup analyses were performed according to recurrence status and receipt of adjuvant chemotherapy.

Results

High FoxP3 expression in IT, PT, and T compartments was significantly associated with shorter OS. Although FoxP3 expression showed significant associations with DFS in Kaplan–Meier analyses, it did not retain independent significance in multivariate models. Tumor-associated stromal FoxP3 expression correlated with increased stromal response and advanced nodal stage, whereas high PT-FoxP3 expression was associated with positive surgical margins. In patients receiving adjuvant chemotherapy, Kaplan–Meier analyses showed no clear survival separation; however, compartment-specific prognostic effects of FoxP3 were preserved in multivariate analyses.

Conclusion

FoxP3-positive lymphocyte infiltration represents a clinically relevant prognostic biomarker in PDAC, with its impact on survival strongly dependent on spatial localization within the tumor microenvironment. Compartment-based evaluation of FoxP3 may improve risk stratification and provide a biologically meaningful framework for future immunologically informed therapeutic strategies in PDAC.