High Expression of PD-L1 Is Associated with Better Survival in Pancreatic/Periampullary Cancers and Correlates with Epithelial to Mesenchymal Transition

Abstract

Periampullary cancers (PACs) are characterized by tumor-infiltrating lymphocytes (TILs), severe fibrosis, and epithelial to mesenchymal transition (EMT). The immune checkpoint marker programmed death-1 (PD-1) and its ligands 1 and 2 have gained popularity in cancers with TILs. Evidence suggests a strong relationship between immune checkpoint markers and EMT in cancers. Here, we evaluated the expression and prognostic significance of immune checkpoint and EMT markers in PAC using an automated image analyzer. Formalin-fixed, paraffin-embedded surgically excised PAC tissues from laboratory archives (1998-2014) were evaluated by immunohistochemical staining for PD-1, PD-L1, and PD-L2 in a tissue microarray. In total, 115 PAC patients (70 males and 45 females) with an average age of 63 years were analyzed. Location, gross type, size, radial resection margin, N-M stage, lymphatic invasion, vascular invasion, perineural invasion, histologically well-differentiated severe inflammation, and high PD-L1 expression were significantly associated with recurrence. Higher PD-L1 expression, but not PD-1 and PD-L2, was significantly related to better overall survival (OS) and disease-free survival (DFS). PD-L1 and PD-L2 were significantly related to EMT markers. Aside from other clinicopathologic parameters, high PD-L1 expression was significantly related to better OS and DFS of PAC patients. Moreover, immune checkpoint markers were significantly associated with EMT markers. Therefore, PD-L1 expression can be a good prognostic marker to guide future immune target-based therapies in PAC patients.

Keywords: disease-free survival; overall survival; programmed death ligand-1; programmed death ligand-2; programmed death-1; recurrence.

Figure 1

Kaplan-Meier plots on the relationship between immune cell markers and overall survival (OS) and disease-free survival (DFS) in the periampullary/pancreatic cancers patients. There was a significant difference between PD-L1 and OS according to (A) PD-L1 (1+:3+ vs. 1+:1+ or 2+), (B) PD-L1 (2+:3+ vs. 2+:2+ vs. 2+:1+), and (C) PD-L1 (2+:3+ vs. 2+:1+ or 2+), while there was also a significant relationship between PD-L1 and DFS according to (D) PD-L1 (2+:3+ vs. 2+:2+ vs. 2+:1+), and (E) PD-L1 (2+:3+ vs. 2+:1+ or 2+).