Dynamic changes of host immune response during Helicobacter pylori-induced gastric cancer development

Helicobacter pylori infection is the main risk factor for gastric cancer (GC). Chronic inflammation is usually induced by H. pylori infection and is accompanied by inherent immune disorders. However, the dynamic changes in the host immune response associated with the transition from normal to metaplasia, dysplasia, and GC are largely undefined.

We established the H. pylori-induced GC mice model. The gastric mucosa of H. pylori-infected mice was subjected to RNA-sequencing analysis at different stages. We analyzed systemic immune disturbances in the spleen and changes in serum inflammatory cytokines during GC development, including gastritis, premalignant lesions (pre-GC), and GC stages.

RNA-sequencing analysis of the gastric mucosa of H. pylori-infected mice highlighted the important role of immune-associated pathways (especially inflammatory pathways) during GC development. Immune cell proportion analysis revealed the stage-dependent involvement of key immune cell types, including increased Th17 cells in early gastritis and pre-GC stages and decreased central memory CD4+ and CD8+ T cells during GC transition. Serum inflammatory cytokine analysis showed that IL-6 and IL-10 levels significantly increased, whereas IL-23 levels decreased during the GC stage.

In summary, we illustrated systemic immune disturbances in the spleen and changes in serum inflammatory cytokines during GC development. Th17 cells were involved in early gastritis and premalignant processes, while central memory T cells participated in GC transition. Our findings provide valuable insights into identifying key inflection points and associated biomarkers for the early detection, diagnosis, and treatment of GC.