Mayo researchers discover immune system blocker at work in kidney cancer

Mayo Clinic researchers have discovered a new and deadly player in the most common form of kidney cancer. They've shown that the molecule B7-H4 helps renal cell carcinoma (RCC) grow and spread by blocking the immune system. The Mayo researchers found that when B7-H4 is active, RCC patients are three times as likely to die from their cancer as RCC patients whose tumors don't express B7-H4.

The findings may one day help physicians predict patient outcome and direct treatment, as well as serve as a target at which to aim new and better therapies for this most lethal urologic malignancy. The findings appear in the current early online edition of Proceedings of the National Academy of Science (http://www.pnas.org/papbyrecent.shtml).

Renal cell carcinoma accounts for 85 percent of all kidney cancers. In the United States, an estimated 35,000 patients are diagnosed with kidney cancer and about 12,000 die from this disease every year. It most commonly occurs in people who are between 50 and 70 years old, and is the eighth most common cancer in men and the 10th most common cancer in women.

Significance of the Mayo Clinic Research

The Mayo researchers uncovered three potentially useful roles for B7-H4:

* As a biomarker for RCC — A biomarker is an indicator that communicates a consistent message to scientists that they can use to plot a course of action. In this case, the message is that cells with active B7-H4 are the most aggressive cancers and need immediate and powerful treatment. Cancer specialists can use this information to quickly match patients with the best form of therapy. Many different biomarkers have been explored; however, few show this type of diagnostic power.

* As a target for future therapies — Mayo Clinic discovered that nearly 82 percent of RCC tumors have active B7-H4 on the blood vessels that nourish tumors, compared to only 6.5 percent of nearby normal renal tissues showing B7-H4. If researchers can design cancer-killing drugs that can target B7-H4 on the tumor vessel, they could cut off the tumor's lifeline.

* As a deadly collaborator — With other members of the B7 family, notably B7-H1, B7-H4 combines forces to block the immune system. The Mayo Clinic team showed that RCC tumors expressing both B7-H4 and B7-H1 pose an even greater threat of death than tumors that express one or the other alone.

“Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic biomarker for patients with RCC,” says investigator Amy Krambeck, M.D. “In addition, B7-H4 represents a new target to attack tumor cells as well as tumor vessels, thus improving treatment options for patients with RCC.”

“For years, researchers have wondered how kidney cancer can disable an attack by the body's immune system,” adds co-investigator R. Houston Thompson, M.D. “Our data help explain how kidney tumors shut down the immune system, which may lead to enhanced targeted therapies for this refractory tumor.”