Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE

  • Cell Death Dis. 2025 Jan 14;16(1):17. doi: 10.1038/s41419-024-07318-w.
Sifan Liu  #  1 ,  Nan Zhang  #  2 ,  Xu Ji  1 ,  Shuyue Yang  1 ,  Zheng Zhao  1 ,  Peng Li  3
Affiliations
  • 1. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease Center, Beijing, 100050, China.
  • 2. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease Center, Beijing, 100050, China. [email protected].
  • 3. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, State Key Laboratory for Digestive Health, National Clinical Research Center of Digestive Diseases, Beijing Digestive Disease Center, Beijing, 100050, China. [email protected].
  • # Contributed equally.
PMID: 39809787 DOI: 10.1038/s41419-024-07318-w
Abstract

Helicobacter pylori (H. pylori) Infection is a well-established risk factor for gastric Cancer, primarily due to its virulence factor, cytotoxin-associated gene A (CagA). Although PD-L1/PD-1-mediated immune evasion is critical in Cancer development, the impact of CagA on PD-L1 regulation remains unclear. This study revealed that H. pylori CagA upregulated squalene epoxidase (SQLE) expression, a key enzyme in the Cholesterol biosynthesis pathway. Elevated SQLE activity increased cellular palmitoyl-CoA levels, enhancing PD-L1 palmitoylation while decreasing its ubiquitination. This ultimately increases PD-L1 stability, suppressing T cell activity and facilitating immune evasion in gastric Cancer. In summary, our findings highlight the crucial role of the CagA-SQLE-PD-L1 axis in gastric Cancer progression, suggesting potential therapeutic strategies for targeting CagA-positive gastric Cancer.

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