According to a study published in Nature, taking aspirin increases the immune response of T cells against malignant tumors. In experiments on mice, scientists have shown that aspirin inhibits the synthesis of thromboxane A2, which suppresses the activity of T lymphocytes. In the future, the researchers suggest including aspirin in combination treatment regimens for cancer metastases.
Metastases are responsible for 90 percent of deaths from malignant neoplasms. The more effectively the immune system fights metastases, the better the prognosis for the patient. This is not an easy task, since cancer cells are able to elude immune defense mechanisms. In some cases, they are helped by thromboxane A2, which is produced by platelets. It narrows blood vessels, increases blood pressure and activates platelet aggregation. In addition, thromboxane A2 suppresses the activity of T-lymphocytes, which reduces the body's ability to recognize and eliminate tumor cells.
In previous studies, scientists have found that daily aspirin intake is associated with reduced metastasis. Aspirin is an inhibitor of cyclooxygenases, which are expressed in many tissues, including platelets. Cyclooxygenase-1 is necessary for the synthesis of thromboxane A2, so scientists hypothesized that aspirin's antimetastatic effect may be due to the suppression of thromboxane A2's inhibitory effect on T cells.
To confirm their hypothesis, Rahul Roychoudhuri from the University of Cambridge and colleagues conducted a study on mice. In previous studies, they selected candidate genes whose switching off in mice leads to a decrease in the number of metastases. One of these genes was ARHGEF1, encoding a guanine exchange factor. It is involved in intracellular signaling cascades, including in immune cells.
In the new study, the scientists switched off the ARHGEF1 gene in T lymphocytes in mice, and these animals showed increased T cell activity in lung and liver metastases, which triggered their rejection (p < 0.0001 and p = 0.01, respectively). In the second part of the experiment, the scientists treated mice with metastases with aspirin. The drug reduced the circulation of thromboxane A2 in the blood of animals, but this was observed only in wild-type mice, and not in those rodents in which the ARHGEF1 gene was switched off in T cells. This means that the effect of aspirin is mediated by immune mechanisms. In addition, wild-type mice treated with aspirin had a reduced number of metastases in the lungs (p = 0.038). The results of the study indicate that aspirin can be used as an additional therapy for cancer metastases. Future studies will be able to test a combination of aspirin with other immunotherapy drugs. Aspirin may also have a direct effect on tumor development. Scientists recently found that daily aspirin intake reduced the risk of hepatocellular carcinoma in patients with nonalcoholic fatty liver disease.
