Abstract
Gastric cancer (GC) is an aggressive malignancy that is the third leading cause of cancer mortality worldwide. Localized GC can be cured with surgery, but most patients present with more advanced non-operable disease. Until recently, treatment options for relapsed and refractory advanced GC have been limited to combination chemotherapy regimens, HER-2 directed therapy, and radiation, which lead to few durable responses. Over the past decade, there have been significant advances in our understanding of the molecular and immune pathogenesis of GC. The infectious agents Epstein-Barr virus and Helicobacter pylori perturb the gastric mucosa immune equilibrium, which creates a microenvironment that favors GC tumorigenesis and evasion of immune surveillance. Insights into immune mechanisms of GC have translated into novel therapeutics, including immune checkpoint inhibitors, which have become a treatment option for select patients with GC. Furthermore, chimeric antigen receptor T-cell therapies have emerged as a breakthrough treatment for many cancers, with recent studies showing this to be a potential therapy for GC. In this review, we summarize the current state of knowledge on immune mechanisms of GC and the status of emerging immunotherapies to treat this aggressive cancer, as well as outline current challenges and directions for future research.