Photo by
Yossi Zeliger/TPS on 9 September, 2023
Scientists Uncover Molecular ‘Bridges’ That Help Breast Cancer Evade Immunity
Jerusalem, 5 November, 2024 (TPS) -- Israeli and American scientists have discovered a potential new approach to treating a particularly aggressive form of breast cancer that could be applied to other types of cancers.
According to the World Health Organization (WHO) and the American Cancer Society, approximately 2.3 million new cases of breast cancer were diagnosed in 2020, making it the most frequently diagnosed cancer worldwide, and about 1 in 8 women will be diagnosed with it at some point in their lives.
Scientists from Israel’s Weizmann Institute of Science and the California-based City of Hope cancer treatment center said their research into the way cancer evades the immune system was inspired by Sun Tzu, a Chinese military strategist who lived in the 5th century BCE. In his still-studied treatise, “The Art of War,” he famously wrote, “Build your enemy a golden bridge to retreat across.”
The study, which was recently published in the peer-reviewed journal, Cell Reports, suggests that some cancerous growths adopt a similar strategy, creating “molecular bridges” to evade immune attacks. This tactic, they found, prevents nearby immune cells from attacking the tumor, effectively suppressing the body’s natural defense mechanism.
Under the leadership of Prof. Idit Shachar, the Weizmann team previously studied similar bridges in blood cancers. They identified a protein, CD84 (also known as SLAMF5), which cancer cells use to establish these molecular connections with nearby noncancerous cells. This bridging process enables cancer cells to thrive and avoid immune attacks.
Following these findings, Shachar’s team developed an antibody that blocks CD84 from creating these connections, which had shown promising results in slowing disease progression in blood cancer.
Building on this earlier research, Dr. Steven Rosen, an executive vice president at City of Hope, suggested investigating whether this molecular bridge-building could play a similar role in other cancers, specifically triple-negative breast cancer (TBNC). This form of breast cancer is notoriously difficult to treat because it lacks certain markers such as estrogen, progesterone, and HER2 receptors that are often targeted in conventional therapies.
TNBC represents approximately 20% of all breast cancer diagnoses and has a higher mortality rate compared to other forms of breast cancer, the researchers said.
Led by Stav Rabani, a doctoral student in Shachar’s lab, the researchers analyzed tissue samples from women with TBNC. They observed that while the cancer cells in these tumors expressed low levels of CD84, they caused surrounding immune cells to express high levels of it. This elevated CD84 expression led to the formation of molecular bridges among the immune cells, which in turn suppressed the immune response, allowing the tumor to grow unchecked.
Further analysis showed that patients with high levels of CD84 in their tumor microenvironment had lower survival rates than those with lower levels.
Armed with these insights, the researchers tested their previously developed CD84-blocking antibody on mice genetically engineered to develop breast cancer.
They discovered that when treated with this antibody, the mice experienced significantly slower tumor growth. In some cases, the treatment even led to complete tumor regression.
Other cancers that exploit similar immune-suppressing tactics might also respond to this approach. Patients might also experience fewer side effects since the antibody works selectively on immune cells with high CD84 expression, leaving most healthy cells unaffected. As the treatment is designed to work specifically in the presence of high CD84 expression, it could be tailored to patients who exhibit this trait within their tumors. But further research and clinical trials will be necessary.
