Good news! Cancer is history (soon)!
"“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 ... 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 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 ... 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. ...
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. ...
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. ...
Next, the researchers studied the progression of breast cancer in mice that had been genetically engineered not to express the CD84 protein and found that these mice developed significantly smaller growths. This finding prompted the scientists to test their previously developed antibody – which had successfully prevented the building of molecular bridges – as a treatment for breast cancer. Injections given twice a week to mice that had started developing breast cancer significantly slowed tumor growth and, in some cases, even led to complete recovery. ..."
From the highlights and abstract:
"Highlights
• CD84 is upregulated in the TNBC microenvironment
• Drives IL-10 expression in Bregs via the β-catenin/Tcf4 pathway
• Enhances immune suppression to increase tumor growth
Summary
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. The tumor microenvironment (TME) plays a major regulatory role in TNBC progression and is highly infiltrated by suppressive immune cells that reduce anti-tumor immune activity. Although regulatory B cells (Bregs) are a key TME component, knowledge of their function in TNBC is limited. CD84 is a homophilic adhesion molecule that promotes the survival of blood tumors. In the current study, we followed the role of CD84 in the regulation of the TME in TNBC. We demonstrate that CD84 induces a cascade in Bregs that involves the β-catenin and Tcf4 pathway, which induces the transcription of interleukin-10 by binding to its promoter and the promoter of its regulator, AhR. This leads to the expansion of Bregs, which in turn control the activity of other immune cells and immune suppression. Accordingly, we suggest CD84 as a therapeutic target for breaking immune tolerance in TNBC."
Graphical abstract
Figure 1 CD84 is overexpressed in the TME of TNBC patients
Cross section of healthy breast tissue (left) and tissue from a patient with triple-negative breast cancer (right). In cancer patients, the cancer cells (light blue) surround microenvironment cells that produce a high level of CD84 (purple)
The cancer warriors at the Weizmann Institute or is it the Miss Israel contest? Just kidding!
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