FOXP3 Expression and the Tumor Microenvironment in Resected Pancreatic Ductal Adenocarcinoma: Association with Clinicopathological Prognostic Factors

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality. FoxP3 expression and the tumor microenvironment (TME) play crucial roles in tumor progression and immune evasion. OBJECTIVES: To investigate the association between FoxP3 expression in intratumoral (IT), peritumoral (PT), and tumor-associated (T) regions, and various clinicopathological prognostic factors in PDAC patients. PATIENTS AND METHODS: Ninety-eight PDAC patients diagnosed between 2015 and 2021 were evaluated. FoxP3 expression was assessed by immunohistochemistry in IT, PT, and T regions. Patients were stratified into high and low FoxP3 expression groups based on median values. Correlations with tumor size, stage, histological differentiation, invasion patterns, lymph node metastasis, and survival outcomes were analyzed. Patients were also grouped according to recurrence status (Ex) or survival (Survived) for further clinicopathological evaluation. RESULTS: High FoxP3 expression in IT, PT, and T regions was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). The T-FoxP3 subgroup demonstrated increased stromal response and higher lymph node metastasis incidence. Elevated PT-FoxP3 expression correlated with positive surgical margins in the Ex group. ROC analysis confirmed that high FoxP3 expression correlated with recurrence. Stromal responses were significantly higher in the Ex group and in patients with high FoxP3 expression. Other clinicopathological variables did not differ significantly between groups. CONCLUSION: FoxP3 expression is a promising prognostic biomarker in PDAC, linked to poorer survival outcomes. Targeting FoxP3 may be beneficial in developing future therapeutic strategies to improve patient prognosis.