Abstract
Simple SummaryGastric cancer is one of the most common malignant tumours worldwide, with the fifth and third highest morbidity and mortality, respectively, of all cancers. Survival is limited, as most of the patients are diagnosed at an advanced stage, and are not suitable for surgery with a curative intent. Chemotherapy has only modestly improved patients’ outcomes and is mainly given with a palliative intent. Immunotherapy has improved overall survival of patients with gastric cancer, and has thus become a new standard of care in clinic. In this review we discuss the strong molecular rationale for the administration of immunotherapy in this disease and analyse the clinical data supporting its use.Gastric cancer has a median survival of 11 months, and this poor prognosis has not improved over the last 30 years. Recent pre-clinical data suggest that there is high tumour-related neoantigen expression in gastric cancer cells, suggesting that a clinical strategy that enhances the host’s immune system against cancer cells may be a successful approach to improve clinical outcomes. Additionally, there has been an increasing amount of translational evidence highlighting the relevance of PD-L1 expression in gastric cancer cells, indicating that PD-1/PD-L1 inhibitors may be useful. Several molecular subgroups of gastric cancer have been identified to respond with excellent outcomes to immunotherapy, including microsatellite instable tumours, tumours bearing a high tumour mutational burden, and tumours related to a chronic EBV infection. In gastric cancer, immunotherapy has produced durable responses in chemo-refractory patients; however, most recently there has been a lot of enthusiasm as several large-scale clinical trials highlight the improved survival noted from the incorporation of immunotherapy in the first line setting for advanced gastric cancer. Our review aims to discuss current pre-clinical and clinical data supporting the innovative role of immunotherapy in gastric cancer.
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