Effective cancer immune therapy through order in the blood vessels

April 21, 2008

Immune therapies are considered very promising in cancer medicine: Tumor-fighting immune cells are supposed to invade tumor tissue and eliminate cancer cells right there. Although this works well in the test tube, clinical application often fails because immune cells are unable to get into the tumor tissue from the bloodstream in sufficient numbers.

This is due, among other things, to the ‘chaotic’ tumor vasculature: To get supplied with nutrients, a tumor stimulates the formation of new vessels. However, the architecture of these newly formed blood vessels differs from the normal one; they are poorly organized and regarded as immature. Therefore, in many tumors, immune cells have difficulty entering the cancer tissue. Studies show, however, that patients survive longer when immune cells are able to invade the tumor.

In an article published in Nature, scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and Heidelberg University Hospitals, jointly with Australian researchers, have now described a key molecule that is responsible for the immature state of the tumor vasculature. In mice suffering from cancer whose gene encoding the Rgs5 signal protein is switched off, the investigators observed a normalization of blood vessels in the tumor. Tumor-specifically activated immune cells that were transplanted into these animals were found to colonize the cancer tissue in large numbers. In contrast, in mice with normal Rgs5 status, there is no significant invasion of immune cells into the tumor.

Survival rates clearly showed the success of the immune therapy: While some of the Rgs5-deficient animals were still alive after 48 weeks into the investigation, all animals with normal Rgs5 formation had died from cancer after 35 weeks at the latest. Vaccination with tumor-specific proteins also resulted in improved survival times of Rgs5-deficient mice, while it showed no effect in control animals.

“We were surprised that a gene that apparently affects vascular structure has such a strong influence on the success of immune therapies. Rgs5 is, thus, a completely new, promising target structure for clinical tumor therapy,” says DKFZ’s Professor Günter Hämmerling, one of the scientists leading the study. “But we don’t necessarily have to knock out Rgs5 to improve the success of immune therapies. Available therapeutics that normalize tumor vasculature should also increase the invasion of immune cells into tumor tissue.”

Citation: Juliana Hamzah, Manfred Jugold, Fabian Kiessling, Paul Rigby, Mitali Manzur, Hugo H. Marti, Tamer Rabie, Sylvia Kaden, Hermann-Josef Gröne, Günter J. Hämmerling, Bernd Arnold and Ruth Ganss: Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature 2008, DOI: 10.1038/nature06868

Source: Helmholtz Association of German Research Centres

Explore further: Shedding light on millipede evolution

Related Stories

Shedding light on millipede evolution

August 2, 2015

As an National Science Foundation (NSF)-funded entomologist, Virginia Tech's Paul Marek has to spend much of his time in the field, hunting for rare and scientifically significant species. He's provided NSF with an inside ...

Out of the lamplight

July 31, 2015

The human body is governed by complex biochemical circuits. Chemical inputs spur chain reactions that generate new outputs. Understanding how these circuits work—how their components interact to enable life—is critical ...

The truth about sharks

July 28, 2015

Danger: shark attack (or more properly, say scientists, shark bite). With sharks swimming ever closer to shore this summer—or seeming to—and crossing paths with surfers and bathers, what's going on?

Researcher uses microscale technology to isolate rare cells

June 17, 2015

In a blood sample taken from a cancer patient, there may be a single circulating tumor cell among hundreds of thousands of other cells. These tumor cells can provide valuable information about how cancer progresses, and could ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.