Controlling Cancer Through Immunotherapy

A group of researchers have revealed that the immune system can inhibit cancer growth without actually killing the cells.

Scientists have for years worked on a technique, known as Immunotherapy, by using the immune system, to eliminate cancer. They found that an alternate approach existed, that is, when immune attacks cannot kill the cancer, it was possible to find ways for the immune system to contain it.

The results also helped explain why some tumours suddenly stop growing and go into a long-lasting period of dormancy.

"Thanks to the animal model we have developed, scientists can now reproduce this condition of tumour dormancy in the laboratory and look directly at cancer cells being held in check by the immune system," Nature magazine quoted co-author Robert Schreiber, Ph.D., Alumni Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis, as saying.

"That will allow us to see if we can model this state therapeutically," he added.

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 tumour.

"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," he added.

More than a century ago, scientists had first projected that the immune system might be able to recognize cancer cells as potentially harmful.

A theory called cancer immunosurveillance, suggested that if this recognition took place, the immune system would attack tumours 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 tumours.

The cancer immunosurveillance theory however fell out of favour and in 2001 a new model known as cancer immunoediting was established.

The cancer immunoediting theory suggests that conflict between cancers and the immune system naturally takes place, but with three different outcomes. Firstly, that the immune system can eliminate cancer and destroy it. Secondly, that the immune system can form a balance with cancer, by checking its growth but not destroying it. Thirdly, that the cancer can escape from the immune system, and become more malignant.

To directly observe dormant tumours in mice, researchers injected them with small doses of a chemical carcinogen. Mice that developed outright tumours were set aside; the remaining mice had small, stable masses at the site of the injections. When certain components of these animals' immune systems were disabled, the small growths became full-blown cancers, suggesting that the immune system had previously been holding the tumours in check.

"We don't think the immune system has evolved to handle cancers," Schreiber notes. "Cancer is typically a disease of the elderly, who have moved beyond their reproductive years, so there probably was no evolutionary pressure for the immune system to find a way to fight cancer."

Equilibrium sometimes may be a more common outcome of tumour-immune encounters than elimination. According to the researchers' theory, some of us may harbour dormant tumours that either developed spontaneously or from exposure to carcinogens. They propose that these quiescent tumours are unleashed only as we age or are exposed to environmental, infectious or physical stresses that cause a breakdown of the immune system.

Researchers are further planning a molecular-level investigation of what happens in tumours and the immune system during equilibrium. They also want to test their results' applicability both in humans and in different types of cancers.

"Over the past decade, remarkable advances have been made in our understanding of how the immune system reacts against cancer and influences the course of the disease, and defining the equilibrium phase of cancer immunoediting represents the newest milestone in these advances," says researcher L. J. Old.

"The challenge now is to incorporate these findings into our thinking about human cancer and to develop immunotherapeutic strategies that complement current methods of cancer treatment," he added.

The study appeared Nov 19 in the advance online publication of Nature.

Source-ANI
MAR/P