Prognostic significance of tumor immune microenvironment and immunotherapy: Novel insights and future perspectives in gastric cancer

World J Gastroenterol. 2018 Aug 28;24(32):3583-3616. doi: 10.3748/wjg.v24.i32.3583.


Despite a decrease in gastric cancer incidence, the development of novel biologic agents and combined therapeutic strategies, the prognosis of gastric cancer remains poor. Recently, the introduction of modern immunotherapy, especially using immune checkpoint inhibitors, led to an improved prognosis in many cancers. The use of immunotherapy was also associated with manageable adverse event profiles and promising results in the treatment of patients with gastric cancer, especially in heavily pretreated patients. These data have led to an accelerated approval of some checkpoint inhibitors in this setting. Understanding the complex relationship between the host immune microenvironment and tumor and the immune escape phenomenon leading to cancer occurrence and progression will subsequently lead to the identification of prognostic immune markers. Furthermore, this understanding will result in the discovery of both new mechanisms for blocking tumor immunosuppressive signals and pathways to stimulate the local immune response by targeting and modulating different subsets of immune cells. Due to the molecular heterogeneity of gastric cancers associated with different clinico-biologic parameters, immune markers expression and prognosis, novel immunotherapy algorithms should be personalized and addressed to selected subsets of gastric tumors, which have been proven to elicit the best clinical responses. Future perspectives in the treatment of gastric cancer include tailored dual immunotherapies or a combination of immunotherapy with other targeted agents with synergistic antitumor effects.

Keywords: Gastric cancer; Immune checkpoint inhibitors; Immunotherapy; Prognostic significance; Tumor immune microenvironment.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biological Products / pharmacology
  • Biological Products / therapeutic use
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Costimulatory and Inhibitory T-Cell Receptors / antagonists & inhibitors*
  • Costimulatory and Inhibitory T-Cell Receptors / immunology
  • Costimulatory and Inhibitory T-Cell Receptors / metabolism
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy / trends
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Prognosis
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / mortality
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology*


  • Antineoplastic Agents, Immunological
  • Biological Products
  • Biomarkers, Tumor
  • Costimulatory and Inhibitory T-Cell Receptors