Aging, Immunity, and Cancer
As people age, their risk of getting cancer and dying from it increases. A recent study shows that people 65 years and older are at highest risk of cancer death compared to other age groups. As the number of people living beyond 65 years expands -- in the United States alone this population segment is expected to more than double from 35 million to 70 million by 2030 -- the need to explore the link between age and cancer grows more urgent.
Probing an unresolved question
Lloyd J. Old, M.D., director of the Cancer Research Institute Scientific Advisory Council and a world-leading tumor immunologist, says research into the link between aging and cancer constitutes one of the most intriguing and potentially important areas of study today.
"A link between aging, immunity, and cancer has long been postulated, but it has not yet been proven," says Old. "We know, for example, that there is an increase in cancer incidence as people age; and we know there is a decrease in the ability of the immune system to protect against infectious disease in older adults. But whether there is a causal relationship between these two facts remains unclear."
According to Old, there is growing support within the field of tumor immunology for the idea that, in healthy individuals, immune control prevents cancer cells from emerging and progressing to dangerous stages of disease. When cancer does develop, it can be considered a failure of the immune system to keep the cancer cells under control.
"The immune system can destroy cancerous cells outright," says Old, "but other times a balancing act ensues between cancer growth and immune control. In experimental systems, the resulting state of equilibrium can be maintained for extended periods, often keeping tumors at undetectable levels. Changes to either side of the equation, however, can tip the careful balance to one side or the other."
The Cancer Research Institute has worked for the past 56 years to advance a new and highly promising class of cancer treatments that seek to restore immune control of cancer. These immunotherapies for cancer, like therapeutic cancer vaccines, monoclonal antibodies, and immune modulators, are emerging as a fourth modality in cancer treatment to complement chemotherapy, radiation, and surgery, and soon will become part of the standard-of-care for cancer patients.
Identifying possible links between cancer and aging
"Age- or disease-related decrease in a person’s immune defenses, for example, may be a factor in disrupting the balance between cancer development and immune control," says Old. "In a weakened state of immune protection, cancer cells gain the advantage and are able to establish a foothold in the body and progress to disease."
Advances in our understanding of the relationship between cancer and the immune system, however, may help researchers to identify and define specific age-related deficiencies in immune protection against cancer development.
"The study of the effect of aging on immunity, particularly in light of the striking advances in our understanding of the immune system, is a high priority for the field. The more we learn about this relationship, the more opportunities will emerge to correct and even prevent age-related immune deficiencies," says Old. Maintaining robust immunity later in life could mean cancer will have a much more difficult time breaking free of immune control.
Tiny creatures help yield enormous new insights
Matthew Youngman, Ph.D., is a CRI-funded postdoctoral fellow who is studying the effects of aging on the immune system. Working in the laboratory of Dennis Kim, M.D., Ph.D., in the department of biology at the Massachusetts Institute of Technology in Cambridge, MA, Youngman seeks to understand the genetic basis of the effect of aging on a highly conserved immune signaling pathway found in humans and Caenorhabditis elegans, a tiny roundworm the size of a comma and that has a lifespan of roughly three weeks.
"Since we want to study something that is at the end of life," Youngman say, "it was important to be in a system that has a pretty short lifespan. We can look at a very, very old worm when it’s only twelve or fifteen days old." Youngman has focused his research on two proteins called PMK-1 and DAF-16/FOXO and their role in protecting the worm against infection throughout different stages of its life. These proteins act as switches that turn on or off processes that lead to production of other proteins that fight infection.
According to Youngman, his research has important implications for understanding the effects of aging on the human immune system. "DAF-16/FOXO has a counterpart in humans that turns out to be a tumor suppressor." His research could lead to new understanding of how the protein’s human counterpart protects people from cancer or, later in life, fails to protect against cancer.
Solving both sides of the equation
Old cautions that correcting or preventing age-related immune deficiencies may not be the solution to reducing cancer in older populations. "Maintaining immune strength is only one side of the equation. Cancer cells have an extraordinary capacity to evade all barriers put in their way, including immunity. Therapeutic strategies that also include tactics to block cancer’s evasive mechanisms likely will be effective ways to establish a durable state of equilibrium between cancer and the immune system."
Such a strategy could potentially halt cancer’s ability to spread, thus diminishing or preventing the damage cancer causes and significantly reducing a patient’s risk of dying from the disease. Tumor immunologists envision cancer will soon become a manageable, chronic disease rather than one that is acutely deadly. "This would represent a major advance in cancer therapy," says Old.
Jill O’Donnell-Tormey, Ph.D., executive director of the Cancer Research Institute, says CRI-funded scientists are making great headway in identifying the different immune-related factors that contribute to cancer progression and control. "Every day, we learn more about the body’s natural defenses against cancer and how cancer can evade those immune defenses," says O’Donnell-Tormey. "CRI researchers are producing new insights that fuel the development of improved strategies to restore immune protection against cancer. As we continue to make progress in both laboratory and clinical research that aims to learn how to harness the immune system’s power to combat cancer, we move closer to bringing this disease under control."