Autotaxin-Lysolipid Pathway: A Target to Reactivate Anti-Tumor Immunity in Pancreatic Cancer
| Type | research |
|---|---|
| Area | Pancreas |
| Published(YearMonth) | 2401 |
| Source | https://www.nature.com/articles/s43018-023-00703-y |
| Tag | newsletter |
| Checkbox | |
| Date(of entry) |
This study uncovers how the autotaxin (ATX) enzyme, a regulator of lysolipid signaling, drives pancreatic cancer progression by suppressing immune cell activity in the tumor microenvironment. ATX-generated lysophosphatidic acid (LPA) inhibits eosinophil recruitment by downregulating CCL11 (eotaxin-1) expression via AP-1 transcription factor suppression. Eosinophils, which were shown to induce tumor cell apoptosis and impede progression, were notably absent in ATX-active tumors. Pharmacologic or genetic ATX inhibition restored eosinophil presence, reduced tumor growth, and enhanced survival in models. Observations in human PDAC samples revealed that individuals with eosinophil-enriched tumors exhibited significantly better outcomes. These findings highlight the ATX–LPA axis as a promising therapeutic target to modulate immune suppression and improve survival in pancreatic cancer.