From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer

Int J Mol Sci. 2018 Dec 20;20(1):13. doi: 10.3390/ijms20010013.

Abstract

Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized.

Keywords: checkpoint inhibitors; esophageal cancer; gastric cancer; immunotherapy; microsatellite instability.

Publication types

  • Review

MeSH terms

  • Animals
  • B7-H1 Antigen / metabolism
  • Combined Modality Therapy
  • Epithelial-Mesenchymal Transition
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / therapy*
  • Gene Expression
  • Humans
  • Immunity*
  • Immunotherapy* / methods
  • Microsatellite Instability
  • Microsatellite Repeats
  • Phenotype
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism
  • Programmed Cell Death 1 Receptor / metabolism
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / therapy*
  • Tumor Escape / immunology*

Substances

  • B7-H1 Antigen
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor