Scientists discover how aspirin could prevent some cancers from spreading

Good news! Cancer is history (soon)!

Just amazing how good old aspirin keeps on giving! When I take my next low dose aspirin today, I will feel much better immediately!

"... 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. ...

The researchers determined that ARHGEF1 suppresses a type of immune cell called a T cell, which can recognise and kill metastatic cancer cells. 

To develop treatments to take advantage of this discovery, they needed to find a way for drugs to target it. The scientists traced signals in the cell to determine that ARHGEF1 is switched on when T cells are exposed to a clotting factor called thromboxane A2 (TXA2).

This was an unexpected revelation for the scientists, because TXA2 is already well-known and linked to how aspirin works. ..."

From the abstract:

"Metastasis is the spread of cancer cells from primary tumours to distant organs and is the cause of 90% of cancer deaths globally. Metastasizing cancer cells are uniquely vulnerable to immune attack, as they are initially deprived of the immunosuppressive microenvironment found within established tumours. 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."

Scientists discover how aspirin could prevent some cancers from spreading | University of Cambridge "Scientists have uncovered the mechanism behind how aspirin could reduce the metastasis of some cancers by stimulating the immune system."

Aspirin prevents metastasis by limiting platelet TXA2 suppression of T cell immunity (open access)

Fig. 5: Aspirin promotes anti-metastatic immunity by releasing T cells from ARHGEF1-dependent suppression by TXA2.