PD-L1 is an independent prognostic predictor in gastric cancer of Western patients

Oncotarget. 2016 Apr 26;7(17):24269-83. doi: 10.18632/oncotarget.8169.

Abstract

Targeting the PD-1/PD-L1 immune checkpoint signaling is a novel promising treatment strategy in several tumor entities, and it is suggested that PD-L1/PD-1 expression is predictive for a PD-1/PD-L1 checkpoint inhibitor treatment response. We investigated the expression of PD-L1 and PD-1 by immunohistochemistry in a large and well characterized gastric cancer (GC) cohort of Caucasian patients, consisting of 465 GC samples and 15 corresponding liver metastases. Staining results were correlated with clinico-pathological characteristics and survival. PD-L1 expression was found in tumor cells of 140 GCs (30.1%) and 9 liver metastases (60%) respectively in immune cells of 411 GCs (88.4%) and 11 liver metastases (73.3%). PD-1 was expressed in tumor infiltrating lymphocytes in 250 GCs (53.8%) and in 11 liver metastases (73.3%). PD-L1 expression was significantly more prevalent in men, GCs of the proximal stomach, unclassified, papillary, Her2/neu-positive, Epstein-Barr-virus-positive, microsatellite instable, and PIK3CA-mutated GCs. A high PD-L1/PD-1 expression was associated with a significantly better patient outcome, and PD-L1 turned out to be an independent survival prognosticator. The correlation of PD-L1/PD-1 expression with distinct clinico-pathological patient characteristics may serve as a surrogate marker of PD-L1-positive GCs and may direct the use of immune checkpoint treatment strategies.

Keywords: immune therapy; pembrolizumab; predictive biomarker; programmed death-1.

MeSH terms

  • Aged
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / immunology
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Prognosis
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Survival Rate
  • White People

Substances

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