Activated CD38+ mast cells promote gastric cancer progression by suppressing CD8+ T cell cytotoxic activity through adenosine metabolism

Helicobacter pylori ( H . pylori ) infection is the primary driver in gastric cancer (GC) development, but the dynamic changes of the gastric mucosal microenvironment during H . pylori -associated GC progression remains elusive. Here, we perform single-cell RNA sequencing (scRNA-seq) on 21 gastric mucosae collected from four typical stages of GC progression under H . pylori infection. Our scRNA-seq analysis delineates the cellular landscape, dissects the dynamic alterations, and characterizes distinct immune cell populations. Notably, H . pylori -associated activated mast cells upregulate CD38 and COX2 expression, leading to increased secretion of adenosine and prostaglandin E 2 (PGE 2 ). PGE 2 enhances adenosine receptor expression in CD8 + T cells, thereby suppressing their cytotoxicity via adenosine signaling. Cellular interactions are more complex at the GC stage than in the premalignant lesions. Collectively, our study offers a comprehensive insight into the evolving gastric mucosal microenvironment and validates the pro-tumor role of activated mast cells under H . pylori infection.