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01-06-99 As a clinical scientist and a certified nutritionist, I probably would have never tried Calorad® if it had not been recommended to me by my best friend, Scott.

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The Immune System Can Drive Cancer Into Dormancy

A multinational team of clinical researchers has demonstrated that the immune system can stop the growth of a cancerous tumor without actually killing the cancer itself.

Scientists have been working for decades to use the innate power of our own immune system to eradicate cancer, using techniques known as immunotherapy or immune enhancement. Our immune system is responsible for seeking out and eliminating damaged or diseased cells as well as cells with genetic mutations, and eliminating these cells from our body. Enhancing immune function enables these specialized cells to do this job more efficiently. The new recently-published findings prove that an alternate to this approach may exist: When the cancer can't be completely killed with attacks by our immune system, it may be possible to use the immune system to contain the growth and spread of a cancer. The results of this study also may help explain why some tumors seem to suddenly stop growing and go into a long period of dormancy.

The study appears in the online publication of Nature.   Nature. 2007 Nov 18

"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," states 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 state between the cancerous cells and the immune system "equilibrium". During equilibrium, the immune system decreases the cancer's ability to replicate and also kills and eliminates some of the cancerous cells, but not quickly and efficiently enough enough to completely destroy or even shrink the size of the tumor.

"We may one day be able to use immunotherapy to artificially induce equilibrium and convert cancer into a chronic but controllable disease," states 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 postulated that our immune system might be able to recognize cancer cells as potentially harmful more than a century ago. Under a theory that is called "cancer immunosurveillance", researchers suggested that if this recognition took place, the immune system would attack tumors in the same manner that it fights invading microorganisms. Immunotherapy uses therapeutic agents to increase the chances that the immune system will recognize and attack tumors.

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

Like the older theory of cancer immunosurveillance, cancer immunoediting proposes that conflict between cancers and the immune system naturally takes place but also suggests that three very different outcomes can result.
  • The immune system can eliminate cancer, destroying it;
  • The immune system can establish equilibrium with cancer, checking the growth of the cancer, but not eradicating it; or
  • The cancer can escape from the immune system, in a process called metastasis, becoming more malignant in the process.
Until this latest study published in Nature, solid evidence for the second outcome, equilibrium, was lacking. Schreiber, Smyth and their colleagues suggested that equilibrium existed primarily on the basis of other physicians' clinical experiences. Evidence that equilibrium exists included reports of cancers that inexplicably go into remission for years. In addition, there have been hints that in a few cases organ transplants have transferred undetected dormant tumors to the new recipients.

To directly observe equilibrium, or the existence of dormant tumors in mice, researchers injected laboratory mice with small doses of a chemical carcinogen. Mice that immediately developed tumors were removed from the test group; the remaining mice had small, stable tumor masses at the site of the injections which did not appear to grow. When certain components of these animals' immune systems were disabled, the small growths became active and growing cancers, suggesting that the immune system of these mice had previously been holding the tumors in check.

"We don't think the immune system has evolved to handle cancers," Schreiber stated. "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."

Schreiber, Smyth and Old speculate that a cancerous cell may look like a cell infected by an invading microorganism to a component of the immune system. To overcome the safeguards that prevent the immune system from attacking the body's own tissues (immune tolerance), a tumor must have a high level of immunogenicity, or ability to provoke an immune reaction. Cancer cells can reduce their immunogenicity by changing the materials they present on their outer surface to the cells of the immune system in order to more closely resemble those materials presented by normal tissue cells. This process enables the third outcome of the immunoediting theory: escape or "metastasis".

Equilibrium sometimes may be a more common outcome of tumor-immune encounters than cancer elimination. According to the researchers' theory, some of us may harbor dormant tumors that may develop spontaneously (by genetic mutation) or from exposure to carcinogens. They propose that these inactive tumors are unleashed only as we age or are exposed to environmental, infectious or physical stresses that cause a weakening or breakdown of the immune system.

These researchers plan a molecular-level investigation of what happens in tumors and the immune system during the process of equilibrium to observe what factors may induce this equilibrium. They also want to test their results' applicability in clinical trials in humans with different types of cancers.

"For example, we need to look at which tissues are regularly edited by the immune system and at how closely the immune system watches over these tissues," Schreiber states. "If you completely knock out the immune system in mice, you'll see tumors spring up in some tissues but not in others, and this suggests that there may be differing levels of immune system monitoring in different tissue types."

"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," Old stated. "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."

Source:, Koebel et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007 Nov 18

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