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

  • Cell Rep. 2026 Feb 24;45(2):116863. doi: 10.1016/j.celrep.2025.116863.
Jiabao Zhao  1 ,  Deyi Feng  2 ,  Fan Zhang  3 ,  Shuntian Cai  4 ,  Yubo Xiong  5 ,  Guangchao Pan  6 ,  Jingsong Ma  5 ,  Jinshui Tan  5 ,  Mengya Zhong  5 ,  Zeyang Lin  7 ,  Yifan Zhuang  5 ,  Wei Wang  5 ,  Huiwen Zhou  5 ,  Shengyi Zhou  5 ,  Ao Cheng  3 ,  Meijuan Xu  5 ,  Wenjie Ye  5 ,  Hangzi Chen  8 ,  Yongxi Song  9 ,  Zhenning Wang  10 ,  Xuehui Hong  11
Affiliations
  • 1. Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, China; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
  • 2. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China.
  • 3. Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Institute of Health Sciences, China Medical University, Shenyang 110001, China.
  • 4. Department of Gastroenterology, Zhongshan Hospital of Xiamen University, Xiamen 361004, China.
  • 5. Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, China.
  • 6. Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, China; School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.
  • 7. Department of Pathology, Zhongshan Hospital of Xiamen University, Xiamen 361004, China.
  • 8. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, China. Electronic address: [email protected].
  • 9. Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Institute of Health Sciences, China Medical University, Shenyang 110001, China. Electronic address: [email protected].
  • 10. Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Institute of Health Sciences, China Medical University, Shenyang 110001, China. Electronic address: [email protected].
  • 11. Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen 361004, China. Electronic address: [email protected].
PMID: 41579372 DOI: 10.1016/j.celrep.2025.116863
Abstract

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 E2 (PGE2). PGE2 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.

Keywords
CP: cancer; CP: immunology; H. pylori; activated mast cell; gastric cancer.
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