Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients with Pancreatic Ductal Adenocarcinoma Treated with Neoadjuvant Chemotherapy

Objectives The aim of this study was to examine tumor-infiltrating lymphocytes (TILs) and their prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy. Methods Intratumoral CD4⁺, CD8⁺, and FOXP3⁺ lymphocytes were examined by immunohistochemistry using a computer-assisted quantitative analysis in 136 PDAC patients who received neoadjuvant therapy and pancreaticoduodenectomy. The results were correlated with clinicopathological parameters and survival. Results High CD4⁺ TILs in treated PDAC were associated with high CD8⁺ TILs (P = 0.003), differentiation (P = 0.04), and a lower frequency of recurrence (P = 0.02). Patients with high CD4⁺ TILs had longer disease-free survival and overall survival (OS) than did patients with low CD4⁺ TILs (P < 0.01). The median OS of patients with a high CD8⁺/FOXP3⁺ lymphocyte ratio (39.5 [standard deviation, 6.1] months) was longer than that of patients with a low CD8⁺/FOXP3⁺ lymphocyte ratio (28.3 [standard deviation, 2.3] months; P = 0.01). In multivariate analysis, high CD4⁺ TILs were an independent prognostic factor for disease-free survival (hazard ratio, 0.49; 95% confidence interval, 0.30-0.81; P = 0.005) and OS (hazard ratio, 0.54; 95% confidence interval, 0.33-0.89; P = 0.02). Conclusions High level of CD4⁺ lymphocytes is associated with tumor differentiation and lower recurrence and is an independent prognostic factor for survival in PDAC patients treated with neoadjuvant therapy.