Tumor protein offs patrolling immune cells - Kill or Be Killed - Brief Article

Science News, June 29, 2002 by J. Travis

Think of cancer as a kind of infection. Like viruses and bacteria, tumor cells can develop ways to avoid detection and destruction by a person's immune system.

Scientists now have found that many human cancers may evade surveillance by exploiting a protein normally found on certain immune cells. In an upcoming Nature Medicine, Lieping Chen of the Mayo Clinic in Rochester, Minn., and his colleagues report that tumor cells bearing this molecule, dubbed B7-H1, spur the death of cancer-fighting immune sentinels called T cells.

This finding may force researchers to rethink so-called cancer vaccines and other cancer-therapy strategies that work by rallying the immune system. "These therapies will be in trouble if the tumor is B7-H1 positive," says Chen. "If you block B7-H1, however, you should improve immunotherapy."

Several years ago, Chen's team identified B7-H1 as a member of a molecular family that regulates the activity of T cells. In their new work, the researchers looked for B7-H1 in a variety of normal tissues. The protein appeared only on the immune cells called macrophages. These cells may use B7-H1 to get rid of excess T cells to protect against autoimmune disorders.

When the investigators looked at cancer cells growing in lab dishes, they detected B7-H1 in several lines derived from lung and ovarian tumors. The protein was even more prominent in tumor samples taken directly from patients with lung, ovarian, and colon cancer and the skin malignancy called melanoma. "When you study surgical samples, the majority ... do express the molecule," says Chen.

The scientists then grew T cells in lab dishes along with breast cancer cells that normally make B7-H1 or with melanoma cells genetically engineered to make the protein. In both cases, the investigators documented that the cancer cells promoted the death of the neighboring T cells.

Chen's team also injected mice with another type of cancer cell genetically engineered to make B7-H1. The resulting tumors grew faster than ones generated by cancer cells lacking the protein.

"We're accumulating quite a list now of potential mechanisms by which tumors escape" destruction, says Alan N. Houghton of Memorial Sloan-Kettering Cancer Center. In most cases, he explains, tumors exploit the body's natural regulation of immune responses.

As for B7-H1's importance, Houghton remains wary. "There's a lot of biology left undone," he says. "We really don't understand why the T cells die."

Chen is now testing in mice whether blocking B7-H1 will boost therapies that rely on the immune system to fight off cancers.