Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group

Oncotarget. 2016 Dec 6;7(49):80426-80434. doi: 10.18632/oncotarget.12603.

Abstract

Gastric adenocarcinoma is one of the most common causes of cancer-related death. In this study, we conducted immunohistochemical studies for PD-L1, PD-1, CTLA-4, and CD8 using tissue microarrays from 464 gastric cancer samples and evaluated the correlations between their expression, clinicopathologic factors, and five-year overall survival. PD-L1 and PD-1 expression was significantly correlated with several adverse prognostic pathologic factors, including higher T-stage, diffuse Lauren histologic type, and lymphatic invasion. Conversely, CTLA-4 expression was correlated with factors of favorable clinical outcomes. A complete case analysis revealed that high PD-L1 and PD-1 expression had an adverse effect on five-year overall survival in univariate analyses. Subgroup analyses wherein patients were divided into two groups according to CD8+ tumor infiltrating lymphocyte levels (high and low) showed that high PD-L1 expression was a significant adverse prognostic factor only in the high CD8+ tumor-infiltrating lymphocytes group. Further research and clinical trials are needed to determine the clinical usefulness of these findings.

Keywords: CTLA-4; PD-1; PD-L1; gastric adenocarcinoma; prognosis.

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Aged
  • B7-H1 Antigen / analysis*
  • Biomarkers, Tumor / analysis*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • CTLA-4 Antigen / analysis
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Programmed Cell Death 1 Receptor / analysis
  • Proportional Hazards Models
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Time Factors
  • Tissue Array Analysis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor