Society of Diabetic Nephropathy Prevention Journal of Preventive Epidemiology 2476-3934 11 2 2026 07 01 Aspirin limits platelet TXA2-mediated suppression of T-cell immunity to prevent cancer metastasis e39330 e39330 10.34172/jpe.2026.39330 EN Kianoush Saberi https://orcid.org/0000-0002-4292-2252 Atieh Okhli https://orcid.org/0000-0002-7858-0362 Khorsid Rigi https://orcid.org/0009-0003-1422-6721 Seyed Amir Banikarim https://orcid.org/0009-0006-0785-9020 Sara Teihou Jorshari https://orcid.org/0009-0002-1763-3392 Niloofar Khosravi https://orcid.org/0000-0002-7274-9817 Zahed Karimi https://orcid.org/0000-0002-2304-6779 Anna Ghorbani Doshantapeh https://orcid.org/0009-0007-1604-9342 Shahnaz Sharifi https://orcid.org/0000-0001-9194-3538 Journal Article 10.34172/jpe.2026.39330 2025 12 29 2026 02 16 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.