the Weizmann Institute of Science previously demonstrated that blood cancer cells rely on “molecular bridges” with neighboring support cells for survival and proliferation.
In a new study, 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.
Historically, cancer treatment primarily aimed to eliminate malignant cells through methods like radiation therapy or chemotherapy. However, recent research has highlighted the crucial role of intercellular communication in tumor growth.
Shachar’s lab at the Weizmann Institute of Science previously demonstrated that blood cancer cells rely on “molecular bridges” with neighboring support cells for survival and proliferation. These bridges, formed by the CD84 protein, allow for direct communication between cancer cells and their environment. By targeting this protein with a specific antibody, researchers were able to disrupt these bridges and slow disease progression.
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Building on these promising results, the Weizmann Institute team has initiated a collaborative effort with the City of Hope cancer center to further explore the therapeutic potential of this approach.
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.
“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.”
