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:
"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."
About the Study
The Mayo Clinic team examined 250 fresh-frozen tumor specimens removed from renal cell carcinoma patients. They sorted the tumors into two groups: those that showed active B7-H4 and those that did not. They then matched this data with information about the clinical outcomes of all the patients. From this comparison of laboratory and clinical data, the pattern emerged associating active B7-H4 with fatal, spreading cancers, compared to tumors lacking B7-H4. The current investigation builds on the Mayo Clinic team's 2004 and 2005 discoveries concerning B7-H1, another immune system blocker, which also may be a useful target at which to aim new therapies.
About the Immune System
The immune system has "stop and go" molecules to regulate it. When it is in "go" mode, it generates an immune attack. Both B7-H1 and B7-H4 stop the attack -- and when regulated properly, are necessary to maintaining good health because they keep the immune system from attacking the healthy body. But the Mayo Clinic research shows that in kidney cancer, B7-H1 and B7-H4 are present in high amounts in the most aggressive tumors and the vessels that feed these tumors. This abnormality suggests that these concentrations may actually keep the immune system from doing its normal job, thus allowing the cancer to grow and spread.
Collaborators and Support
Other members of the Mayo Clinic research team included: Haidong Dong, M.D., Ph.D.; Christine Lohse; Eugene Park; Susan Kuntz; Bradley Leibovich, M.D.; Michael Blute, M.D.; John Cheville, M.D.; and Eugene Kwon, M.D. Their work was supported by The Richard M. Schulze Family Foundation, The Commonwealth Foundation for Cancer Research, the Helen and Martin Kimmel Foundation, and Mayo Clinic.
To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories. For more on Mayo Clinic research, go to www.mayo.edu.
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