Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms23084147
Keywords
gastric cancer; STAT1; PD-L1
Funding
- China Scholarship Council (CSC)
- Ministry of Education of the China [CSC202006010387]
- Bayerisches Hochschulzentrum fur China (BayCHINA)
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [395357507-SFB 1371]
- German Federal Ministry of Education and Research (BMBF) [German Research Presence in Asia] [01DO17022]
- Capital's Funds for Health Improvement and Research [CFH 2020-2-1026]
- PKU-Baidu Fund [2020BD034]
Ask authors/readers for more resources
Helicobacter pylori infection activates the JAK-STAT signaling pathway and upregulates PD-L1 expression, leading to immune suppression and contributing to the development and progression of gastric cancer. The activation of STAT1 and upregulation of PD-L1 are associated with premalignant lesions, immune infiltration, and poor prognosis.
Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis and has been identified as a major risk factor for the development of gastric cancer (GC). Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling mediates immune regulatory processes, including tumor-driven immune escape. Programmed death ligand 1 (PD-L1) expressed on gastric epithelium can suppress the immune system by shutting down T cell effector function. In a human cohort of subjects with gastric lesions and GC analyzed by proteomics, STAT1 increased along the cascade of progression of precancerous gastric lesions to GC and was further associated with a poor prognosis of GC (Hazard Ratio (95% confidence interval): 2.34 (1.04-5.30)). We observed that STAT1 was activated in human H. pylori-positive gastritis, while in GC, STAT1, and its target gene, PD-L1, were significantly elevated. To confirm the dependency of H. pylori, we infected gastric epithelial cells in vitro and observed strong activation of STAT1 and upregulation of PD-L1, which depended on cytokines produced by immune cells. To investigate the correlation of immune infiltration with STAT1 activation and PD-L1 expression, we employed a mouse model of H. pylori-induced gastric lesions in an Rnf43-deficient background. Here, phosphorylated STAT1 and PD-L1 were correlated with immune infiltration and proliferation. STAT1 and PD-L1 were upregulated in gastric tumor tissues compared with normal tissues and were associated with immune infiltration and poor prognosis based on the TCGA-STAD database. H. pylori-induced activation of STAT1 and PD-L1 expression may prevent immune surveillance in the gastric mucosa, allowing premalignant lesions to progress to gastric cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available