Overview
- A Science paper published Thursday reports that many tumours release the enzyme peroxiredoxin 1 (PRDX1) into the tumour interstitial fluid where it removes reactive oxygen species (ROS) that T cells need to switch on.
- The study shows small amounts of ROS are required for T cell receptor signaling and that extracellular PRDX1 lowers T cell ROS, disrupting their activation and weakening anti‑tumour immunity.
- Researchers used CRISPR to delete Prdx1 in multiple mouse cancer models and found increased T cell activity, slower tumour growth, spontaneous rejection in a melanoma model, and restored responses to immune checkpoint drugs in formerly resistant tumours.
- Analyses of human cancer cell‑line secretomes, gene expression across thousands of tumours, and measurements of patient tumour fluid all found tumour‑derived PRDX1, indicating the mechanism may operate in people but remains untested in clinical trials.
- The authors propose targeting this 'redox checkpoint' with neutralizing drugs, inhibitors or engineered immune cells as a new path for immunotherapy while warning patients not to change treatments or take antioxidants based on these preclinical results.