Neoadjuvant Chemoradiotherapy Enhances Tumor PD-L1 Expression in Pancreatic Cancer

Background/Aim: Programmed cell death-1 (PD-1) and its ligand PD-L1 play crucial roles in cancer-related immunosuppression. Previous reports have hinted at the potential of neoadjuvant chemoradiotherapy (NACRT) to shift the immunosuppressive microenvironment of pancreatic adenocarcinoma (PDAC) toward an immunogenic state in selected patients. This study aimed to assess the effects of NACRT on PD-L1 expression and PD-1⁺ lymphocyte infiltration in PDAC.

Patients and Methods: Eighty-two patients with PDAC underwent surgical resection. Among them, 55 patients with borderline-resectable PDAC (BR-PDAC) received NACRT, while 27 patients with resectable PDAC underwent straightforward resection without NACRT. Using immunohistochemical staining, resected specimens were examined to assess PD-1⁺ tumor-infiltrating lymphocytes (TILs), CD8⁺ TIL, forkhead box P3 positive (Foxp3⁺) TILs, and PD-L1 expression in tumor cells.

Results: High PD-L1 expression correlated positively with NACRT treatment and inversely with PD-1⁺ TILs. A high CD8⁺ TILs level was strongly correlated to PD-L1 expression. The numbers of PD-1⁺ TILs and Foxp3⁺ TILs were significantly correlated in the straight-line group but not in the NACRT group. In both groups, no significant correlation was found between the overall survival of patients and PD-1⁺ TILs or PD-L1 expression alone.

Conclusion: NACRT in pancreatic cancer may affect TILs and PD-L1 expression, thereby improving the immunosuppressive microenvironment and implying a potential synergy between checkpoint inhibitors and radiation treatment.