Current Status of Immunotherapy in Gastroesophageal Cancer

Abstract

Gastroesophageal cancers comprising gastric cancer (GC) and cancers of the distal esophagus and gastroesophageal junction (GEJ) are a global health threat. In Western populations, the incidence of GC is declining which has been attributed to effective strategies of eradicating Helicobacter pylori infection. To the contrary, GEJ cancers are on the rise, with obesity and reflux disease being viewed as major risk factors. During the past decade, perioperative chemotherapy, pre- or postoperative radiochemotherapy, and, in Asian populations, adjuvant chemotherapy were shown to improve the outcome of patients with advanced GC and GEJ cancers suited for surgery. Less progress has been made in the treatment of metastatic disease. The introduction of novel immunotherapeutic agents like the monoclonal antibody trastuzumab in patients with HER2-positive disease has marked a turning point. Recently, several novel pharmacological agents targeting growth factor receptors, angiogenic pathways, adhesion molecules, and mediators of intracellular signal transduction have been clinically explored. In addition, strategies using so-called immune checkpoint inhibitors to enhance the immunological response against tumor cells, which showed promising long-lasting responses in different types of cancers, are currently tested in several clinical trials in GC and GEJ. Antigen-specific active immunotherapies and cellular therapies have been less explored. Their future role in clinical management of advanced GC/GEJ remains to be defined. Here we summarize the current status and future developments of immunological treatment options in GC and GEJ cancer.