“Build your enemy a golden bridge to retreat across” is a piece of advice offered by Sun Tzu in his ancient military treatise, The Art of War. It turns out that cancerous growths adopt this strategy in their battle against the immune system. In a new study being published in Cell Reports, researchers from Prof. Idit Shachar’s laboratory at the Weizmann Institute of Science have discovered that a certain type of aggressive breast cancer prompts nearby immune cells to build “molecular bridges” between themselves, which causes these cells to refrain from attacking the cancer and leads to immune suppression. An antibody treatment that blocks the building of these bridges was shown to restore the immune system’s ability to attack with force, inhibiting the cancer’s progression in a mouse model.

In the past, cancer treatment focused on destroying the malignant cells by, for example, using radiation treatment or chemotherapy. In recent decades, however, it has become evident that a tumor’s development depends on the communication between the cancer and the nearby noncancerous cells. In an earlier study, researchers from Shachar’s lab in Weizmann’s Systems Immunology Department showed that blood cancer cells create “molecular bridges” with nearby support cells in order to survive and proliferate – otherwise they die within a matter of days. The researchers identified a protein, CD84 (SLAMF5), that is used to construct these bridges: When this protein is present on the surface of a specific immune cell, it can bind to a similar protein on a different cell, creating an intercellular bridge. In the type of blood cancer studied, CD84 is expressed in high quantities on the cancerous cells themselves, creating physical bridges between these cells and adjacent ones. The researchers even developed an antibody that blocks the bridges, slowing down the disease. As a result of these findings, the scientists began collaborating with the City of Hope cancer treatment and research center in California.

“We then wanted to see whether the molecular bridges between cells in the tumor’s microenvironment are also important in types of cancer other than blood malignancy,” Shachar says. “Dr. Steven Rosen, an executive vice president at City of Hope, proposed that we examine samples from patients with the most aggressive type of breast tumors – triple-negative breast cancer. One of the reasons there is still no cure for these tumors is that their cells show no external signs that would allow us to identify and destroy them. That’s why it is especially important to find a treatment that can suppress the cancer by affecting a component of its supportive microenvironment, rather than the cancer cells themselves.”

In the new study, led by Stav Rabani, a doctoral student in Shachar’s lab, the researchers analyzed the genetic sequences of growths taken from women with triple-negative breast cancer and discovered that the level of CD84 expression in the tumor microenvironment was much higher than normal. One of the surprising findings of the study was that even though breast cancer cells themselves express very low levels of CD84, they cause nearby immune cells to express it in large quantities and to create bridges between themselves, suppressing the immune response. The researchers also found that patients with higher levels of CD84 in their tumors did not survive as long as others.