ISG15/GRAIL1/CD3 axis influences survival of patients with esophageal adenocarcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.A new pathway involving ISG15 and GRAIL1 degrades CD3, reducing T cell activity and worsening survival in esophageal adenocarcinoma (EAC). This immunosuppression mechanism offers potential therapeutic targets for EAC patients.
Area Of Science
- Oncology
- Immunology
- Molecular Biology
Background
- Esophageal adenocarcinoma (EAC) is characterized by immunosuppression, correlating with poor overall survival (OS).
- Upstream factors potentially influencing T cell activity and CD3 levels may drive EAC immunosuppression and survival outcomes.
Purpose Of The Study
- To investigate a pathway impacting CD3 protein stability and T cell activity in EAC.
- To identify molecular mechanisms contributing to immunosuppression and poor survival in EAC.
Main Methods
- Analysis of clinical data and patient samples from Barrett's esophagus to EAC progression.
- Gene expression (RNA-Seq) and protein expression (tissue microarray) analysis.
- Cell biology studies to delineate the CD3 degradation pathway.
Main Results
- Loss of CD3-ε expression and reduced CD3+ T cells correlated with worse OS in EAC.
- The GRAIL1 isoform degraded CD3 proteins and inactivated T cells, while GRAIL2 stabilized them.
- Interferon-stimulated gene 15 (ISG15) facilitated GRAIL1-mediated CD3 degradation.
Conclusions
- An ISG15/GRAIL1/mutant p53 amplification loop negatively impacts CD3 levels and T cell activity.
- This pathway promotes immunosuppression in esophageal adenocarcinoma.
- Targeting this loop may offer therapeutic strategies for EAC.
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