PD-L1 expression in pancreatic ductal adenocarcinoma is a poor prognostic factor in patients with high CD8 + tumor-infiltrating lymphocytes: highly sensitive detection using phosphor-integrated dot staining

Int J Clin Oncol. 2017 Aug;22(4):726-733. doi: 10.1007/s10147-017-1112-3. Epub 2017 Mar 18.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. For the development of more effective immunotherapies, it is first necessary to elucidate the immunological escape mechanisms. In this study, we applied our recently developed highly sensitive immunostaining method employing fluorescent phosphor-integrated dot (PID) nanoparticles to evaluate the prevalence of programmed death ligand 1 (PD-L1) in patients with PDAC.

Methods: This study included 42 patients with PDAC who underwent pancreatectomy. We evaluated PD-L1 expression in these patients using PID staining and correlated PD-L1 expression level with each patient's clinico-pathological features.

Results: PD-L1 expression was detected in 61.9% (26/42) of the patients with PDAC by PID staining. There was a significant difference in overall survival between PD-L1-positive and PD-L1-negative patients [hazard ratio (HR) 2.07, 95% confidence interval (CI) 1.00-4.54; P = 0.049]. Among CD8+-tumor-infiltrating lymphocyte-positive cases, the overall survival of PD-L1-positive patients was significantly poorer than that of PD-L1-negative patients (HR 3.84, 95% CI 1.59-10.35; P = 0.003). Univariate and multivariate analyses indicated that PD-L1 expression was an independent predictive poor prognostic factor in patients with PDAC.

Conclusions: PD-L1 expression appears to be an important prognostic factor in patients with PDAC who underwent surgical resection.

Keywords: Immunohistochemistry; PD-L1; Pancreatic adenocarcinoma; Phosphor-integrated dots.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology*
  • Adenocarcinoma / surgery
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Pancreatic Ductal / surgery
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / surgery
  • Prognosis
  • Staining and Labeling / methods
  • Survival Analysis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human