Cancerous mice given sildenafil – the active ingredient in Viagra – survive more than twice as long as untreated animals, scientists have discovered.
Many tumors cause chronic inflammations which suppress specific attacks against the tumor by the immune system. But a team at the German Cancer Research Center and Medical Faculty Mannheim at Heidelberg University have now shown in mice with melanoma that sildenafil cancels this suppression.
“We distinguish between two different types of immune response. On the one hand, cells of the immune system specifically attack tumor cells. On the other, however, almost every tumor causes in its microenvironment a chronic inflammatory immune response which suppresses the specific antitumor immunity,” says Professor Dr Viktor Umansky.
“Our aim is to reduce the chronic inflammations and, thus, to support the immune system in actively fighting the cancer.”
Umansky used transgenic mice that spontaneously develop a type of skin cancer which is very similar to human melanoma, and detected inflammatory mediators such as interleukin-1-β and interferon-γ. These attract what are called myeloid-derived suppressor cells (MDSC) – known to inhibit the immune system’s most important tumor-specific fighters, the T cells.
When the researchers exposed T cells obtained from the spleen of a healthy mouse to MDSC in the culture dish, the T cells stopped proliferating and reduced the level of an important activating molecule.
“This shows that tumor-specific T cells are actively suppressed by myeloid-derived suppressor cells,” saysUmansky.
The melanoma mice were then given sildenafil, already reported to improve tumor immunity in experimental animal models. And, after seven weeks, more than twice as many of these mice were alive than those which hadn’t had the sildenafil.
Indeed, in the treated animals, both the number of tumor-specific T cells and the level of activating molecules had returned to normal. It seems that the sildenafil successfully neutralized the inflammation and countered the immunosuppressive activity of MDSC.
“Our research approach is special because the disease takes a very similar course in mice as melanoma does in humans,” says Umansky.
“Therefore, it is very well possible that sildenafil can also inhibit the immunosuppressive effects of inflammation and thus improve antitumor immunity in people with melanoma. In this way, the drug may contribute to achieving better treatment results in malignant melanoma.”
