Jiabao Zhao, Deyi Feng, Fan Zhang, Shuntian Cai, Yubo Xiong, Guangchao Pan, Jingsong Ma, Jinshui Tan, Mengya Zhong, Zeyang Lin, Yifan Zhuang, Wei Wang, Huiwen Zhou, Shengyi Zhou, Ao Cheng, Meijuan Xu, Wenjie Ye, Hangzi Chen, Yongxi Song, Zhenning Wang, Xuehui Hong
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.