Targeting the aHSC-PGE2-NK cell axis overcomes immunosuppression and inhibits liver metastasis in fibrotic liver - PubMed
3 hours ago
- #fibrosis
- #liver metastasis
- #immunosuppression
- Liver metastasis (LM) is a major cause of cancer-related mortality, driven by interactions between tumor cells and the liver microenvironment.
- Liver fibrosis, orchestrated by activated hepatic stellate cells (aHSCs), enhances LM by promoting early tumor colonization.
- Prostaglandin E2 (PGE2) secreted by aHSCs disrupts natural killer (NK) cell immune surveillance, facilitating LM.
- Depletion of aHSCs or pharmacological inhibition of COX-2 with Celecoxib (CLX) restores NK cell function and suppresses LM.
- CLX treatment synergizes with anti-NKG2A immunotherapy, boosting efficacy against LM in fibrotic liver, offering a therapeutic strategy.