The presence and level of expression of a cell marker called B7-H1 strongly predicts aggressiveness and mortality for patients with renal cell carcinoma, according to an article published online December 7th by the Proceedings of the National Academy of Sciences (USA). In the study, patients who had higher levels of B7-H1 on their tumor cells were nearly five times more likely to die from the disease than patients with low levels or an absence of the molecule.

The cell marker had previously been identified on healthy immune cells and some other cancers, but not healthy or malignant kidney cells. B7-H1 suppresses immune system activity, and it may act pathologically by allowing tumor cells to grow and spread without triggering an immune response. The current study is also the first to tie this type of cell marker to the clinical parameters of disease 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,” explained Eugene Kwon, MD, senior author of 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 the Mayo Clinic. They found that when patients expressed the marker on their tumor cells, they were at markedly increased risk both of metastasis and death 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,” Kwon said.

One immediate result of the current findings will be research to see how to tie marker levels with treatment choices such as immunotherapy with agents such as Interleukin-2 and alpha interferon.

Furthermore, the researchers noted that a drug 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.

“That’s why we’re so interested in this molecule,” concluded 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.”