Aspirin May Help Prevent Cancer Spread by Boosting Immune Response, Study Finds

Published in Nature, the study conducted in mice revealed that aspirin affects platelets—tiny blood cells responsible for clotting—by reducing the production of thromboxane A2 (TXA2), a clotting factor that suppresses immune T cells. With lower TXA2 levels, T cells regain their ability to target and destroy cancer cells attempting to spread, suggesting a potential role for aspirin in cancer prevention.

"The findings uncover a new way in which the immune system is suppressed, limiting T cells from fighting cancer spread. This helps explain how aspirin may prevent metastasis and could lead to better immunotherapy treatments for stopping cancer from spreading," the researchers wrote.

Metastasis occurs when cancer cells spread from the original tumor to other parts of the body and is responsible for 90% of cancer-related deaths worldwide. As these spreading cells leave the protective environment of the primary tumor, they become more exposed to immune attack. Researchers are exploring ways to use this immune weakness to prevent cancer from returning in patients with early-stage cancer at risk of metastasis.

Against the above background, Rahul Roychoudhuri, Department of Pathology, University of Cambridge, Cambridge, UK, and colleagues showed that COX-1 inhibitors, such as aspirin, boost the immune system's ability to fight cancer metastasis by preventing platelet-derived thromboxane A2 from suppressing T cells.

The researchers found that thromboxane A2 plays a key role in suppressing T-cell activity by activating an immunosuppressive pathway involving the guanine exchange factor ARHGEF1. This process weakens T cell receptor-driven signaling, reducing their ability to proliferate and attack cancer cells. Their experiments in mice showed that deleting Arhgef1 in T cells enhanced their activation at metastatic sites, leading to immune-driven rejection of lung and liver metastases. Further, the researchers demonstrated that limiting TXA2 through aspirin, selective COX-1 inhibitors, or platelet-specific COX-1 deletion reduced metastasis rates, highlighting the critical role of ARHGEF1-dependent TXA2 signaling in this process.

"The study identifies thromboxane A2 as a key regulator of T cell immunity, highlighting its role in cancer prevention and treatment. The findings help explain how aspirin fights metastasis and suggest ways to use it more effectively. Additionally, they open the door for developing new therapies to prevent the spread of cancer," the researchers concluded.

Reference:

Yang, J., Morris, B. I., Contursi, A., Trajkovski, D., Xu, J., Patrascan, I., Benson, J., Evans, A. C., Conti, A. G., Dahmani, L., Zhang, B., Okkenhaug, H., Whiteside, S. K., Imianowski, C. J., Wesolowski, A. J., Webb, L. V., Puccio, S., Tacconelli, S., Bruno, A., . . . Roychoudhuri, R. (2025). Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity. Nature, 1-10. https://doi.org/10.1038/s41586-025-08626-7