Immune System Controls Cancer, Promotes Tumor Dormancy

Newswise — Cancer Research Institute (CRI) supported scientists have proven that dormant cancer cells are actively kept in check by the immune system, while those that escape go on to develop into clinically detectable tumors. A paper online in this week's Nature identifies a crucial stage in the battle, at which point immune defenses stall the expansion of cancer cells that may have managed to dodge past early immunosurveillance.

CRI Scientific Advisory Council Associate Director Robert D. Schreiber, Ph.D., alumni professor of pathology and immunology at Washington University School of Medicine in St. Louis, MO, and CRI supported colleagues there, in collaboration with CRI supported researchers and others at five other academic institutions in Australia, Europe, and the U.S., describe in the paper how they used a mouse model to show that the animal's immune system can keep tumor growth in check over an extended period.

"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 Dr. Schreiber.

In 2001, Dr. Schreiber and colleagues published the first evidence that the immune system is involved in the control of cancer via a process called immunosurveillance. Their most recent paper describes a revised version of this idea, called immunoediting, which the authors say can result in three possible outcomes: "elimination," in which the immune system destroys the cancer; "equilibrium," where the immune system checks cancer's growth but is unable to eradicate it; and "escape," in which cancer cells evade the immune system's defenses and, in the process, often become more malignant.

"We may one day be able to use immunotherapy to artificially induce equilibrium and convert cancer into a chronic but controllable disease," says co-author Mark J. Smyth, Ph.D., professor of the Cancer Immunology Program at the Peter MacCallum Cancer Centre in Melbourne, Australia.

"Drs. Schreiber and Smyth and their colleagues have long been working to establish animal models that demonstrate that the immune system is, in fact, able to keep cancer under control," Cancer Research Institute Executive Director Jill O'Donnell-Tormey, Ph.D., says. "It's one of the key premises underpinning the entire field of cancer immunology, and this additional proof is a major boost to the field."

Clinicians have suspected the existence of such an "equilibrium" state, because dormant cancers sometimes become active when inadvertently transferred from a donor to an immunosuppressed recipient during organ transplantation. It could also explain why some cancers suddenly stop growing and go into a lasting period of dormancy.

Dr. O'Donnell-Tormey is enthusiastic about the role her organization has played in making the discovery possible. "The Cancer Research Institute has supported the Schreiber and Smyth laboratories for many years, providing several million dollars to train graduate students and fund postdoctoral fellows assisting with projects including this latest study," says O'Donnell-Tormey.

She says her organization will also play a significant role in translating the discovery into clinical applications. "Through our Cancer Vaccine Collaborative, a joint program with the Ludwig Institute for Cancer Research, CRI can influence how clinical researchers around the world design clinical trials of their immune-based therapies. Some treatments might seek to promote cancer elimination, while others might aim for equilibrium. We may learn that some patients are more likely to respond better to one type of vaccine versus the other."

"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 CRI Scientific Advisory Council Director Lloyd J. Old, M.D., chairman of the Ludwig Institute for Cancer Research and one of the authors of the paper. "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."

In a News & Views article that was published with the Nature paper, Cornelis Melief, M.D., Ph.D., of the Leiden University Medical Center in The Netherlands and member of the CRI/LICR Cancer Vaccine Collaborative, comments on the "startling results" and says they demonstrate that considering cancer as a fatal disease is not always appropriate.

"Our organization's view, and the view of a growing number of people involved with tackling cancer, is to begin thinking of the disease as a chronic, manageable problem like diabetes or high blood pressure rather than a fatal one," says O'Donnell-Tormey.

SOURCE: Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD. Adaptive immunity maintains occult cancer in an equilibrium state. Nature, Advanced Online Publication, www.nature.com Nov. 18, 2007, http://dx.doi.org/10.1038/nature06309EMBARGOED until Nov. 18, 2007, 1800 London time / 1300 US Eastern time

About the Cancer Research InstituteThe Cancer Research Institute (CRI) is the world's only non-profit organization dedicated exclusively to the support and coordination of scientific and clinical efforts that will lead to the immunological treatment, control, and prevention of cancer. Guided by a world-renowned Scientific Advisory Council that includes five Nobel Prize winners and thirty members of the National Academy of Sciences, CRI supports cutting-edge cancer research at top medical centers and universities throughout the world.

As the initiator and steward of unprecedented global laboratory and clinical programs like the Cancer Vaccine Collaborative, a partnership with the Ludwig Institute for Cancer Research, and the Coordinated Cancer Initiatives, the Cancer Research Institute is ushering in a new era of scientific progress, hastening the discovery of effective cancer vaccines and other immune-based therapies that are providing new hope to cancer patients.

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