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Aspirin as an anti-cancer agent? Its inhibition disrupts the cancer-promoting actions of platelets.
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Scientists have uncovered the mechanism behind how aspirin could reduce the metastasis of some cancers by stimulating the immune system.
They say that discovering the mechanism will support ongoing clinical trials, and could lead to the targeted use of aspirin to prevent the spread of susceptible types of cancer, and to the development of more effective drugs to prevent cancer metastasis.
The scientists caution that, in some people, aspirin can have serious side-effects and clinical trials are underway to determine how to use it safely and effectively to prevent cancer spread, so people should consult their doctor before starting to take it.
Studies of people with cancer have previously observed that those taking daily low-dose aspirin have a reduction in the spread of some cancers, such as breast, bowel, and prostate cancers, leading to ongoing clinical trials. However, until now it wasn’t known exactly how aspirin could prevent metastases.
Open access paper:
Aspirin prevents metastasis by limiting platelet TXA2suppression of T cell immunity
Metastasis is the spread of cancer cells from primary tumours to distant organs and is the cause of 90% of cancer deaths globally1,2. Metastasizing cancer cells are uniquely vulnerable to immune attack, as they are initially deprived of the immunosuppressive microenvironment found within established tumours3. There is interest in therapeutically exploiting this immune vulnerability to prevent recurrence in patients with early cancer at risk of metastasis. Here we show that inhibitors of cyclooxygenase 1 (COX-1), including aspirin, enhance immunity to cancer metastasis by releasing T cells from suppression by platelet-derived thromboxane A2 (TXA2). TXA2 acts on T cells to trigger an immunosuppressive pathway that is dependent on the guanine exchange factor ARHGEF1, suppressing T cell receptor-driven kinase signalling, proliferation and effector functions. T cell-specific conditional deletion of Arhgef1 in mice increases T cell activation at the metastatic site, provoking immune-mediated rejection of lung and liver metastases. Consequently, restricting the availability of TXA2 using aspirin, selective COX-1 inhibitors or platelet-specific deletion of COX-1 reduces the rate of metastasis in a manner that is dependent on T cell-intrinsic expression of ARHGEF1 and signalling by TXA2 in vivo. These findings reveal a novel immunosuppressive pathway that limits T cell immunity to cancer metastasis, providing mechanistic insights into the anti-metastatic activity of aspirin and paving the way for more effective anti-metastatic immunotherapies.
https://www.nature.com/articles/s41586-025-08626-7
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