A NEW study reveals that inhibitors of cyclooxygenase 1 (COX-1), including the common drug aspirin, could enhance immune responses to cancer metastasis, offering hope for preventing recurrence in early-stage cancer patients at risk of spreading disease.
Metastasis, the spread of cancer cells from primary tumours to distant organs, is responsible for 90% of cancer deaths worldwide. The study, conducted in mice, shows that metastasizing cancer cells are particularly vulnerable to immune attack because they lack the immunosuppressive microenvironment of established tumours. Researchers found that platelet-derived thromboxane A2 (TXA2) plays a key role in suppressing the immune system by inhibiting T cell function. TXA2 triggers an immunosuppressive pathway that relies on the guanine exchange factor ARHGEF1, impairing T cell receptor-driven signalling, proliferation, and effector functions.
When researchers deleted ARHGEF1 in T cells, they observed increased T cell activation at metastatic sites, leading to the immune-mediated rejection of lung and liver metastases. Inhibiting TXA2, either through aspirin, selective COX-1 inhibitors, or by removing COX-1 from platelets, reduced the rate of metastasis in mice, in a process reliant on T cell-intrinsic ARHGEF1 expression and TXA2 signalling.
These findings shed light on a new immunosuppressive pathway that limits T cell immunity to cancer metastasis, highlighting aspirin’s potential in reducing metastasis and paving the way for more effective anti-metastatic immunotherapies.
Helena Bradbury, EMJ
Reference
Yang J et al. Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity. Nature. 2025; doi: 10.1038/s41586-025-08626-7.
