In a breakthrough study published in Cell Reports, researchers from Professor Idit Shachar’s laboratory at the Weizmann Institute of Science have identified a novel approach to treating aggressive breast cancers.
The team found that a specific type of breast cancer, triple-negative breast cancer, encourages nearby immune cells to form “molecular bridges,” which suppresses the immune response and allows the cancer to thrive.
By blocking these bridges with a specialized antibody, scientists were able to restore immune function and slow the cancer’s growth in a mouse model.
Traditional cancer treatments like chemotherapy and radiation focus directly on killing cancer cells. But recent research has shown that a tumor’s growth often depends on how it interacts with surrounding noncancerous cells, known as the tumor microenvironment.
This study takes advantage of that idea by targeting the supportive cells around the tumor, rather than the cancer cells themselves.
The team focused on a protein called CD84, which was first identified by Shachar’s lab as a key player in blood cancers. In those cases, CD84 on cancer cells helped create molecular bridges with nearby cells, helping the cancer survive.
Now, the researchers found that even though breast cancer cells themselves express very low levels of CD84, they influence nearby immune cells to produce high levels of the protein.
These immune cells then connect to each other through these molecular bridges, which leads to a suppressed immune response, allowing the cancer to grow unchecked.
Working with City of Hope’s cancer research center, Shachar’s team analyzed tissue from women with triple-negative breast cancer, finding that CD84 levels were significantly higher in the tumor environment than in healthy tissue.
They also discovered that patients with higher levels of CD84 in their tumors tended to have worse outcomes, suggesting that the presence of these molecular bridges is associated with more aggressive disease.
To test the effect of blocking these bridges, the researchers used a mouse model in which the CD84 protein was genetically removed. These mice developed much smaller tumors, suggesting that CD84 is essential for the cancer to progress.
Building on this, the team then administered their CD84-targeting antibody to mice with early-stage breast cancer. The treatment, given twice weekly, significantly slowed tumor growth and even led to complete recovery in some cases.
One surprising discovery was that regulatory B cells, a type of immune cell not typically associated with cancer, also play a role.
In the tumor environment, these cells form additional molecular bridges and produce a protein that signals T cells—cells that normally attack cancer—to stand down. This prevents T cells from targeting the cancer, further weakening the immune response.
The antibody treatment developed by Shachar’s team targets cells with high CD84 levels. Because healthy cells typically have little to no CD84, the treatment focuses only on the affected immune cells in the tumor environment, reducing the risk of side effects.
As Shachar explains, this approach could potentially help a wide range of cancer patients by targeting the microenvironment around tumors, rather than focusing directly on the cancer cells.
In an era of personalized medicine, this strategy offers a promising new direction for treating aggressive cancers like triple-negative breast cancer, with hopes of future applications in other types of tumors.
If you care about breast cancer, please read studies about a major cause of deadly breast cancer, and common blood pressure drugs may increase death risk in breast cancer.
For more information about cancer, please see recent studies that new cancer treatment could reawaken the immune system, and results showing vitamin D can cut cancer death risk.
The study was published in Cell Reports.
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