Immune system can drive cancers into dormant state

A multinational team of researchers has shown for the first time that the immune system can stop the growth of a cancerous tumor without actually killing it.

Scientists have been working for years to use the immune system to eradicate cancers, a technique known as immunotherapy. The new findings prove an alternate to this approach exists: When the cancer can't be killed with immune attacks, it may be possible to find ways to use the immune system to contain it. The results also may help explain why some tumors seem to suddenly stop growing and go into a lasting period of dormancy.

The study appears today in the advance online publication of Nature.

"Thanks to the animal model we have developed, scientists can now reproduce this condition of tumor dormancy in the laboratory and look directly at cancer cells being held in check by the immune system," says co-author Robert Schreiber, Ph.D., Alumni Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis. "That will allow us to see if we can model this state therapeutically."

The study's authors call the cancer-immune system stalemate equilibrium. During equilibrium, the immune system both decreases the cancer's drive to replicate and kills some of the cancerous cells, but not quickly enough to eliminate or shrink the tumor.

"We may one day be able to use immunotherapy to artificially induce equilibrium and convert cancer into a chronic but controllable disease," suggests co-author Mark J. Smyth, Ph.D., professor of the Cancer Immunology Program at the Peter McCallum Cancer Centre in Melbourne, Australia. “Proper immune function is now appreciated as another important factor in preventing the development of some cancers. Further research and clinical validation of this process may also turn established cancers into a chronic condition, similar to other serious diseases that are controlled long-term by taking a medicine."

Scientists first proposed that the immune system might be able to recognize cancer cells as potentially harmful more than a century ago. Under a theory that came to be called cancer immunosurveillance, researchers suggested that if this recognition took place, the immune system would attack tumors with the same weapons it uses to eliminate invading microorganisms. Current immunotherapy efforts use therapeutic agents to increase the chances that the immune system will recognize and attack tumors.

But cancer immunosurveillance has been controversial. The theory had begun to fall out of favor over the years, and in 2001, Schreiber, graduate students Vijay Shankaran and Gavin Dunn, and Lloyd Old, M.D., director of the New York branch of the Ludwig Institute for Cancer Research, proposed a major revision. They called their new model cancer immunoediting.

Like the older theory, cancer immunoediting suggests that conflict between cancers and the immune system naturally takes place but proposes that three very different outcomes can result. The immune system can eliminate cancer, destroying it; the immune system can establish equilibrium with cancer, checking its growth but not eradicating it; or the cancer can escape from the immune system, likely becoming more malignant in the process.