Protein linked to brain metastases

A study published on August 31, 2026, in Neuro-Oncology by a team from the Wake Forest University School of Medicine identified a protein, SIRPα, that helps the most aggressive forms of triple-negative breast cancer colonize the brain.

Brain metastases are serious complication

Brain metastases remain one of the most serious developments of the disease due to the lack of treatments capable of effectively crossing the brain's barrier. In triple-negative breast cancer, the absence of three receptors that treatments typically target makes it one of the most aggressive and difficult forms to treat.

SIRPα correlates with poor prognosis

Researchers found that SIRPα is present more frequently in brain metastases, and higher levels of the protein correlate with a darker prognosis for patients. SIRPα usually serves as a tolerance signal that immune cells read as "do not eat me," but in this context, the tumor appropriates it.

SIRPα affects tumor behavior

The protein acts on two fronts: it pushes cancer cells to produce more fibronectin, a structural protein that lines their environment, and it fragments mitochondria, the cell's energy centers, which increases tumor cell mobility. Exposed to fibronectin, microglia—immune cells that patrol the brain—lose their ability to trigger inflammation intended to repel intruders.

Tumor turns immune cells against them

The tumor thus turns the sentinels meant to fight it into allies. In animal models, reducing or neutralizing SIRPα slowed tumor growth, decreased the amount of cancer found in the brain, and delayed the appearance of metastases.

Blockage restores brain's defenses

The blockage even reversed the state of immunosuppression that protected the sick cells, restoring part of the brain's defenses. The immune cells then rediscovered the tumor and reignited inflammation.

Further research needed

These results remain preliminary and require confirmation in humans. Researchers now plan to test molecules targeting SIRPα, in the hope of offering an option to patients whose tumors spread to the brain.