Researchers Discover Molecule Allowing Cancer to Spread

Mayo Clinic researchers have discovered that a molecule - B7-H1 - may serve as "molecular armor," protecting kidney cancer tumors and repelling assaults by the immune system. Its protection enables renal cell carcinoma to grow and to spread. Renal cell carcinoma is the most common form of kidney cancer and has no cure. The findings appear in the current online edition of Cancer.

The researchers found elevated levels of B7-H1 not only in the primary site of renal cell carcinoma tumor, but also in the metastatic deposits that spread the cancer to other sites in the body. That confirmed the molecule's protection carried beyond the initial tumor. The investigators report 26 cases of surgically examined metastatic renal cell carcinoma. Of these metastatic tumors, 54 percent showed elevated levels of B7-H1, compared to 44 percent of primary tumor sites with elevated B7-H1.

Significance of the Research

A year ago the same Mayo Clinic research team was the first to report that renal cell carcinoma patients with high levels of B7-H1 in their tumors were nearly five times more likely to die from the disease than patients with low levels or an absence of B7-H1. The additional finding reported here is important because it suggests new drug-design strategies. Blocking B7-H1, as already demonstrated in laboratory animals, may one day lead to better care for human cancer patients.

"The immune system has stop-and-go molecules to regulate it," explains Mayo investigator R. Houston Thompson, M.D. "When it's in 'go' mode this generates an immune attack. B7-H1 is one of the molecules that stops the attack, and is necessary in health to keep the immune system from attacking the healthy body. But in kidney cancers - even in the metastatic deposits that spread - B7-H1 is present in high amounts. Our findings suggest that these concentrations may actually keep the immune system from doing its normal job, and that's why the cancer takes over."

Impact on Patient Care

This new knowledge of the B7-H1 molecule could work in several therapeutic ways:

• To develop a drug to block B7-H1 to improve the effectiveness of immunotherapy. Several animal studies show that B7-H1 can be used as a therapeutic target for an antibody that would bind it up and block its function. This could potentially improve treatment responses of patients with kidney cancer by protecting their immune system from being shut down.

• To serve as a biomarker to determine prognosis. High levels of B7-H1 in a tumor biopsy would indicate a poor prognosis; low levels or absence would suggest a good prognosis.

• To help physicians select the best therapy. For example, it's possible that patients with low levels of B7-H1 may be the best candidates for immunotherapeutic treatment using agents such as Interleukin-2 (IL-2) and alpha interferon.

About Renal Cell Carcinoma

Renal cell carcinoma accounts for approximately 85 percent of all kidney cancers. In the United States, an estimated 35,000 patients each year are diagnosed with kidney cancer and approximately 12,000 will die from it. It is the eighth most common cancer in men, the tenth most common in women, and is the sixth leading cause of cancer death. The primary treatment for patients with advanced kidney cancer is IL-2, the only FDA-approved immunotherapeutic agent to stimulate the immune system.

But this treatment is relatively toxic and can further sicken the patient - and only 15 percent to 20 percent of patients respond. Eighty to 85 percent of patients are not significantly helped by it but are exposed to its toxicity.

"That's why we're so interested in this," says Mayo immunologist Eugene Kwon, M.D. "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 other agents by manipulating B7-H1 appropriately. We could improve treatment outcomes, hopefully, and that's what's drastically needed for this disease."