Gastric Cancer in the Era of Immune Checkpoint Blockade

Figure 1

Immune contexture in the pathogenesis of gastric cancer. (a) The colonization of H. pylori in the normal gastric mucosa triggers an inflammatory response with accumulation of neutrophils and inflammatory macrophages and production of proinflammatory cytokines such as IL-1β, IL-8, IL-6, and TNF-α; leading to Th1 polarization, IFN-γ production, and chronic gastritis. (b) In later stages, H. pylori induces the overexpression of PD-L1 in epithelial cells of the gastric mucosa as an immune evasion mechanism, characterized by an increase in regulatory T cells, myeloid-derived suppressor cells (MDSCs), and IL-10 production. (c) Gastric cancer cells express PD-L1 and CD155 which after interacting with PD-1 and TIGIT on the surface of cytotoxic T cells induce T-cell exhaustion and promote the development of an anti-inflammatory tumor microenvironment. (d) Epstein–Barr virus- (EBV-) positive gastric cancer lesions are mainly located in the proximal stomach and are characterized by amplification and, consequently, high PD-L1 and PD-L2 expression with a prominent immune cell infiltration (created with BioRender.com).