Key molecule helps identify renal cell carcinoma

Nov 30 2004

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, http://www.pnas.org.

• 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."