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Using Viagra to Combat Malignant Melanoma
Many tumors cause chronic inflammations, which, in their turn, suppress specific
attacks against the tumor by the immune system. Scientists at the German Cancer
Research Center (DKFZ) and Medical Faculty Mannheim at Heidelberg University have
now shown in mice with melanoma that sildenafil – the active ingredient in Viagra® –
cancels the suppression of the specific immune response. Cancerous mice treated
with the drug survived more than twice as long as untreated fellow animals.
At first it sounds like good news: The body’s own immune system gets active in almost every
cancer – however, not necessarily for the benefit of the patient. “We distinguish between two
different types of immune response,” says Professor Dr. Viktor Umansky, immunologist at
DKFZ and University Medical Center Mannheim. “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.”
In an inflammatory immune response, immune cells of a certain type migrate into the tumor
environment and release characteristic immune mediators. “Our aim is to reduce the chronic
inflammations and, thus, to support the immune system in actively fighting the cancer,”
Umansky said.
He and his team have now studied chronic inflammation as it is caused by malignant
melanoma. For their research, they used genetically-modified (transgenic) mice that
spontaneously develop a type of skin cancer which is very similar to human melanoma. In
the tumor environment and in metastatic lymph nodes of the animals, the investigators
detected inflammatory mediators such interleukin-1-β and interferon-γ. These immune
mediators attract what are called myeloid-derived suppressor cells (MDSC). These immune
cells are known to inhibit the immune system’s most important tumor-specific fighters, the T
cells.
What exactly happens when T cells get under the influence of MDSC? 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. Moreover, the T cells reduced the level of an important
activating molecule. “This shows that tumor-specific T cells are actively suppressed by
myeloid-derived suppressor cells,” said Umansky, explaining their findings.
The melanoma mice were then given sildenafil. This substance, which is better known under
its trade name, Viagra®, had already been reported to improve tumor immunity in
experimental animal models several times before. Of the mice that had been given the
substance with their drinking water, more than twice as many were still alive after about
seven weeks as of their untreated fellows. In the animals that had been treated, both the
number of tumor-specific T cells and the level of activating molecules had returned to normal.
This means that sildenafil successfully neutralizes the chronic inflammation in the melanoma
environment and combats 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,” Viktor Umansky said explaining the medical relevance of his
findings. “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.” A picture for this press release is available on the Internet at: Source: Dr. Alexandra Sevko, German Cancer Research Center Picture legend: MDSC (myeloid-derived suppressor cells) suppress the tumor-specific immune response Christiane Meyer, Alexandra Sevko, Marcel Ramacher, Alexandr V. Bazhin, Christine S. Falk, Wolfram Osen, Ivan Borrello, Masashi Kato, Dirk Schadendorf, Michal Baniyash and Viktor Umansky: Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model. Proceedings of the National Academy of Science (PNAS) USA, 2011; DOI: 10.1073/pnas.1108121108 The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), employing over 2,500 staff members, is the largest biomedical research institute in Germany. More than 1,000 scientists are working to investigate the mechanisms of cancer development, identify cancer risk factors and develop new strategies for better cancer prevention, more precise diagnosis and effective treatment of cancer patients. In addition, the staff of the Cancer Information Service (KID) provides information about this widespread disease for patients, their families, and the general public. DKFZ is funded by the German Federal Ministry of Education and Research (90%) and the State of Baden-Wuerttemberg (10%) and is a member of the Helmholtz Association of National Research Centers. Dr. Stefanie Seltmann Head of Press and Public Relations German Cancer Research Center Im Neuenheimer Feld 280 D-69120 Heidelberg T: +49 6221 42 2854 F: +49 6221 42 2968 presse@dkfz.de

Source: http://www.dkfz.de/en/presse/pressemitteilungen/2011/download/dkfz_pm_11_60_e.pdf