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Using Viagra to combat malignant melanoma
Date:11/8/2011

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 substan
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Contact: Dr. Sibylle Kohlstdt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

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