Combined assessment of stromal tumor infiltrating lymphocytes and tumor peroxiredoxin 4 expression improved prognostic stratification in postoperative pancreatic cancer patients.

Abstract

BACKGROUND: Pancreatic cancer (PC) is characterized by profound immunosuppression and marked biological heterogeneity. Stromal tumor-infiltrating lymphocytes (TILs) reflect host antitumor immunity, whereas peroxiredoxin 4 (PRDX4) represents tumor redox adaptation. However, their combined prognostic value remains unclear. METHODS: We retrospectively analyzed 138 resected cases of PC. Stromal TIL density was assessed on hematoxylin-eosin (H&E) sections, and tumor PRDX4 expression was evaluated by immunohistochemistry. Both markers were dichotomized into high and low groups using ROC-derived thresholds. Patients were further classified into four integrated subgroups: TIL-high/PRDX4-low (TH-PL), TIL-high/PRDX4-high (TH-PH), TIL-low/PRDX4-low (TL-PL), and TIL-low/PRDX4-high (TL-PH). Associations with clinicopathological features and disease-specific survival (DSS) were analyzed. RESULTS: High TIL density was associated with less advanced pathological stage and significantly improved DSS, whereas high PRDX4 expression correlated with lymphovascular and perineural invasion as well as advanced stage. An inverse association between TILs and PRDX4 was observed. Integrated subgroup analysis revealed distinct prognostic patterns: the TL-PH subgroup showed the poorest DSS, whereas the TH-PL subgroup demonstrated the most favorable outcomes. In multivariable Cox models, the TL-PH subgroup remained an independent adverse prognostic factor for both 3- and 5-year DSS, while the TH-PL subgroup showed a protective effect, particularly at 3 years. CONCLUSIONS: Stromal TILs and PRDX4 appear to capture complementary immune and redox features of PC. Their combined assessment may improve prognostic stratification and help to identify a potential redox-associated, immune-excluded subgroup with particularly poor outcomes.