Flaws in our Defense System

Keith Jerome’s research on virus-infected cells provides clues on how viruses and cancer elude capture by the body’s immune system

For Dr. Keith Jerome, the most intriguing question about cancer is not what causes it but why our bodies fail to defend us from the disease after it strikes.

“Infection with a cold virus brings on a very noticeable immune response — congestion, nasal swelling — all of which is part of the infection-fighting process to clear the virus from the body,” said Jerome, an immunologist at Fred Hutchinson Cancer Research Center. “Yet for many cancers, there are no obvious signs of an immune reaction, despite the fact that cancer cells clearly don’t look normal.”

That paradox first struck Jerome while he was a graduate student at Duke University about 15 years ago, where he made a surprising discovery in women with breast cancer. When he extracted their lymph — a clear fluid that carries infection-fighting cells through the body — Jerome found immune cells that reacted against a substance found on breast-cancer cells.

The immune cells he identified are known as T cells, infection-fighters that destroy virus-infected and other unhealthy cells.

“It had been thought previously that the immune system couldn’t see tumors,” said Jerome, also an assistant professor at the University of Washington. “So the question then turned to: Why isn’t the immune system working to recognize and kill tumors when they arise in the body?”

Today in his own laboratory at Fred Hutchinson, Jerome’s research is yielding insight into this and other immune-system shortcomings that cause serious human health problems. Understanding how some diseases evade our body’s defense system may help explain the incomplete control of chronic viral infections by the immune system, the lack of success of current vaccination approaches to many viruses, and the inability of the immune system to control many tumors.

Jerome’s research primarily focuses on the human herpes virus, one of nature’s wiliest — and most common — infections. He uses the microbe as a model system to probe for chinks in the immune-system armor that may be common to many types of immune failure.

“Another example where you see immune failure is with viral infections,” he said. “We see that a lot with our bone-marrow and stem-cell transplant patients, whose immune systems are compromised. Even among healthy individuals, some of us control some infections, while others don’t.”

Uncovering how viruses evade the immune system

That’s particularly true with herpes virus infections.

“A lot of people infected with herpes virus never know it, yet others have obvious symptoms and frequent recurrences,” he said. “It’s clear that the virus has ways to deal with the immune system.”

Viruses are so skilled at escaping immune capture because they have evolved together with humans over millions of years, Jerome said.

“They’ve had plenty of time to probe for our weak spots,” he said. “If we can learn why we can’t completely control viral infections, we will likely learn many things about ourselves. We expect that what we learn about viral immune evasion will be relevant to other examples of immune failure, including cancer.”

In the last few years, Jerome’s lab has discovered two tricks used by the herpes virus to elude capture by the immune system. Both have strong implications for cancer patients. This knowledge could lead to therapies that overcome immune failure in cancer and viral infections or that dampen the hyperactive immune response that causes autoimmune diseases, such as lupus and rheumatoid arthritis.

“When we understand how a virus shuts off an immune cell,” he said, “we may be able to develop therapies that could ultimately benefit cancer patients.”

Barbara Berg, Ph.D., is senior science writer for Fred Hutchinson Cancer Research Center.

Applying viral studies in the real world to help cancer patients

Fred Hutchinson’s Dr. Keith Jerome puts his studies of immune-system evasion to use with patients in his clinical practice at the Seattle Cancer Care Alliance, where he diagnoses infections in patients undergoing bone-marrow and stem-cell transplants for blood cancers. The Alliance is the cancer-treatment partnership of Fred Hutchinson, UW Medicine and Children’s Hospital and Regional Medical Center.

Jerome heads the clinic’s Viral PCR lab, which provides same-day testing for viral infections that most commonly plague patients with compromised immune systems.

Transplant patients, as well as those who receive high-dose chemotherapy for solid cancers, have weakened immune systems unable to cope with a variety of viral, bacterial and fungal infections.

“For a lot of the viruses, we need to catch infections at the earliest whiff of viral activation,” Jerome said. “If you wait even a week with patients in this immunocompromised state, a simple infection can become an almost untreatable problem.”

Almost all of the lab’s tests — which are based on highly sensitive techniques for detecting tiny amounts of viral genetic material — were developed by the laboratory, which processes samples for patients across the country.

“Part of the lab’s function is service work, but we are also on the lookout for the new diseases that may be likely to affect our patient population,” he said. “For example, when the West Nile virus surfaced, we developed a test in record time — about a month.”

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Lifesaving research like that of Dr. Keith Jerome depends on private donations. Financial support from individuals, corporations and charitable foundations provide “seed money” — investments in early phases of research with great promise. These private investments enable our scientists to launch new research for better ways to prevent, diagnose and treat cancer.

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