Researchers at Wake Forest University School of Medicine announced on September 18, 2026 that they identified how a protein called SIRPα helps triple-negative breast cancer (TNBC) spread to the brain while evading the immune system, publishing the findings in the journal Neuro-Oncology. Corresponding author David R. Soto-Pantoja, PhD, Associate Professor of Cancer Biology, said: “The biology of brain metastasis is incredibly complex, and we urgently need better ways to prevent and treat it. Our findings suggest that SIRPα helps make tumor cells more aggressive while also changing the brain environment in ways that help those cells survive.”
A Two-Part Mechanism Inside Cancer Cells
Triple-negative breast cancer is an aggressive subtype that lacks the three markers targeted by common breast cancer treatments and has a greater tendency than other breast cancers to spread to the brain, where treatment options remain limited and outcomes are often poor. The research team found that SIRPα works within cancer cells in two ways: it triggers mitochondrial fission, which increases the cells’ mobility and ability to spread, and it increases production of fibronectin, a protein that weakens the response of the brain’s own immune cells, known as microglia. Soto-Pantoja explained the second effect: “One of the most intriguing findings was that the tumor cells appeared to weaken the response of the brain’s immune cells. This creates a more favorable environment for cancer cells to grow and survive, and SIRPα appears to play an important role in that process.”
From Lab Bench to a Potential Treatment Target
The team reached its conclusions by examining human breast cancer data and tumor samples alongside laboratory experiments involving cancer cells, immune cells, and mitochondria, using preclinical models designed to reproduce brain metastasis. Reducing or inhibiting SIRPα slowed tumor growth and delayed brain metastases in those preclinical models, and researchers now plan to investigate whether blocking SIRPα could enhance the effectiveness of existing immunotherapies or other TNBC treatments. The study was supported by funding including a National Cancer Institute grant (R21CA249349), an American Society for Radiation Oncology-Breast Cancer Research Foundation Career Development Award, the Lewis-Michael Miracle Fund, an Atrium Health Wake Forest Baptist Comprehensive Cancer Center Brain Tumor Center of Excellence Pilot Award, an American Cancer Society Post-Baccalaureate Training Program grant, and a National Cancer Institute Intramural Research Program grant.
