According to a study published in Nature, aspirin increases the T-cell immune response against malignant tumors. In mouse experiments, scientists demonstrated that aspirin inhibits the synthesis of thromboxane A2, which suppresses T-cell activity. In the future, the researchers propose incorporating aspirin into combination treatment regimens for cancer metastases.
Metastases are responsible for 90 percent of cancer-related deaths. The more effectively the immune system fights metastases, the better the patient's prognosis. This is no easy task, as cancer cells are adept at evading immune defense mechanisms. In some cases, thromboxane A2, a hormone produced by platelets, helps them. It constricts blood vessels, increases blood pressure, and activates platelet aggregation. Furthermore, thromboxane A2 suppresses T-cell activity, which reduces the body's ability to recognize and eliminate tumor cells.
In previous studies, scientists found that daily aspirin intake is associated with a reduction in 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 the scientists hypothesized that aspirin's antimetastatic effect may be related to the suppression of the inhibitory effect of thromboxane A2 on T cells.
To confirm their hypothesis, Rahul Roychoudhuri of the University of Cambridge and his colleagues conducted a study in mice. In previous studies, they had identified candidate genes whose silencing in mice led to a reduction in metastases. One of these genes was ARHGEF1, which encodes guanine exchange factor. It is involved in intracellular signaling cascades, including in immune cells.
In a new study, scientists knocked out the ARHGEF1 gene in T lymphocytes in mice. These animals showed increased T cell activity in lung and liver metastases, triggering 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 animals' blood, but this was observed only in wild-type mice, not in those with the ARHGEF1 knockout gene in T cells. This suggests that aspirin's effect is mediated by immune mechanisms. Furthermore, wild-type mice treated with aspirin had a reduced number of lung metastases (p = 0.038). The study's results suggest that aspirin could be used as an adjunctive therapy for cancer metastases. Future studies could test a combination of aspirin with other immunotherapy agents. Aspirin may also directly influence tumor development. Scientists recently found that daily aspirin intake reduces the risk of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease.
