Aspirin limits platelet TXA2-mediated suppression of T-cell immunity to prevent cancer metastasis

Abstract

Aspirin, a widely used non-steroidal anti-inflammatory drug, has shown promise in cancer prevention and reducing metastatic progression. This medication limits platelet thromboxane A2 (TXA2)-mediated suppression of T-cell immunity, thereby preventing cancer metastasis. Platelets, beyond their role in hemostasis, actively contribute to tumor progression and metastasis by various mechanisms, including shielding circulating tumor cells from immune surveillance and promoting their extravasation. One critical pathway involves platelet-derived TXA2, a potent lipid mediator that can directly suppress anti-tumor T-cell responses. TXA2 promotes immune evasion by inhibiting T-cell activation and proliferation, thus hindering the body’s ability to effectively eliminate cancerous cells. Aspirin’s well-known inhibitory effect on cyclooxygenase-1 (COX-1) is key here, as COX-1 is responsible for TXA2 synthesis in platelets. By irreversibly acetylating COX-1, aspirin effectively reduces TXA2 production. Then, the reduction in platelet TXA2 alleviates its immunosuppressive effects on T-cells, thereby restoring and enhancing anti-tumor immunity. The enhanced T-cell activity can then more effectively target and destroy circulating tumor cells, finally limiting the formation of secondary tumors and preventing metastasis.

Keywords: Aspirin, Thromboxane A2, Cancer, Cyclooxygenase-1