New help for tailoring treatments -
Mayo Clinic researchers have discovered a key molecule that lets doctors identify one of the most aggressive types of kidney
cancer. Patients with renal cell carcinoma who have higher levels of a molecule known as B7-H1 in their tumors are nearly
five times more likely to die from the disease than patients with low levels or an absence of the molecule.
This key finding can help to improve treatment of the disease, or to serve as a target for new therapies. The findings are
published in today's online issue of the Proceedings of the National Academy of Sciences, pnas.
Significance of the Mayo Clinic Research
-- This is the first time this molecule has been demonstrated to be expressed on kidney cancers. Prior to the Mayo Clinic
investigation researchers knew that B7-H1 is usually found on immune cells and is found in some other cancers, but is not
found on the healthy kidney.
-- When B7-H1 is expressed, it shuts down the immune system, limiting the body's ability to attack the tumor and perhaps
increasing a tumor's ability to grow and spread.
-- This is the first time that this kind of molecule has been correlated with clinical cancer progression and risk of death.
"Many people have hypothesized that if a cancer makes B7-H1, that cancer may be more aggressive because B7-H1 knocks down the
host's immune system, thereby permitting the tumor to grow without interference from the immune system," explains Eugene
Kwon, M.D., the immunologist and urologist who led the study. "But there has been no evidence at the clinical level to
demonstrate tumors that express B7-H1 are aggressive, so there's been no way to prove this hypothesis."
Dr. Kwon's group studied 196 samples from kidney tumors of patients treated at Mayo Clinic. They found that when patients
express this molecule on their kidney cancer cells, they are at markedly increased risk both of the cancer spreading, and of
dying from the cancer. "We found that when you have high levels of this molecule, your risk of dying from this cancer goes up
almost five-fold," Dr. Kwon says.
Implications of Research
This molecule seems suited to be used as a biomarker by physicians to determine prognosis, according to the Mayo researchers.
High levels of the molecule would indicate a poor prognosis, while low levels or its absence would suggest a good prognosis.
The level of this molecule could also be used to help select the most effective treatments. For example, it's possible that
patients with high levels of B7-H1 may be the best candidates for immunotherapeutic treatment using agents such as
Interleukin-2 (IL-2) and alpha interferon.
Furthermore, say the researchers, a drug developed to block B7-H1 could theoretically be created to improve the effectiveness
of immunotherapy. For instance, an antibody could be developed that would bind B7-H1 and block its function. By doing so,
either alone or in combination with standard therapy, this would potentially improve treatment responses of patients with
kidney cancers by protecting their immune system from being shut down.
About Kidney Cancer
There are different kinds of kidney cancers. Renal cell carcinoma accounts for approximately 85 percent of all kidney
cancers. In the United States, an estimated 35,000 patients will be diagnosed with kidney cancer and approximately 12,000
will die from this disease every year. It is the eighth most common cancer in men and the 10th most common cancer in women.
In the United States, it is the sixth leading cause of cancer death.
The primary treatment for advanced kidney cancer -- Interleukin 2 -- has significant limitations. It is relatively toxic, can
further sicken the patient and only elicits a response in 15-20 percent of all patients treated. This means 80-85 percent of
patients are not significantly helped by it, but nonetheless exposed to its toxicity.
"That's why we're so interested in this molecule," says Dr. Kwon. "We think that by recognizing that B7-H1 may be an
immune-suppressive molecule, we might be able to make patients much more receptive or responsive to immunotherapy using
either IL-2 or some of the other agents that are out there just by manipulating B7-H1 appropriately. We could improve
treatment outcomes, hopefully, and that's what's drastically needed for this disease."
Collaborators and Support
In addition to Dr. Kwon, members of the Mayo Clinic research team included: R. Houston Thompson, M.D., Michael Gillett, M.D.,
John Cheville, M.D., Christine Lohse, Haidong Dong, M.D. Ph.D., W. Scott Webster, M.D., Kent Krejci, M.D., John Lobo, M.D.,
Shomik Sengupta, M.D., Leiping Chen, M.D. Ph.D., Horst Zincke, M.D. Ph.D., Michael Blute, M.D., Scott Strome, M.D., and
Bradley Leibovich, M.D.
To obtain the latest news releases from Mayo Clinic, go to mayoclinic/news. MayoClinic (mayoclinic) is available as a resource for your health stories.
Contact: Bob Nellis
newsbureaumayo
507-284-5005
Mayo Clinic