Advances in immuno-oncology biomarkers for gastroesophageal cancer: Programmed death ligand 1, microsatellite instability, and beyond

World J Gastroenterol. 2018 Jul 7;24(25):2686-2697. doi: 10.3748/wjg.v24.i25.2686.


Blockade of the programmed death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction (GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability (MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatment-refractory solid tumors with MSI status and the third-line or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.

Keywords: Gastric cancer; Immunotherapy; Microsatellite instablility; Programmed cell death 1; Programmed death ligand 1.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Clinical Trials, Phase I as Topic
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / pathology
  • Humans
  • Microsatellite Instability*
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology
  • Treatment Outcome


  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor