Ludwig Lausanne’s Leire Bejarano and Johanna Joyce presented in a January paper in Cancer Cell a granular portrait of how the cellular and molecular components of the blood vessels of lung-, melanoma-, and breast cancer-brain metastases differ from those of healthy brain tissue and how they help shape the tumor microenvironment. The researchers conducted a deep analysis of the cells that form the blood-brain barrier in noncancerous brain tissue and metastatic brain tumor samples freshly isolated from patients. They then focused on endothelial cells (ECs), which line the inner vascular surface, and mural cells—pericytes and smooth muscle cells—that swaddle and stabilize blood vessels. Their analysis revealed multiple aberrations in tumor vessels, including impaired intercellular junctions and adhesiveness of ECs and mural cells that were recapitulated in mouse models of brain metastasis. The murine studies revealed that mural cells and ECs regulate immune cell trafficking into brain metastases. The researchers then focused on CD276, which was highly expressed in ECs and mural cells. CD276 supports immune evasion by cancer cells and is associated with poor patient outcomes. Leire, Johanna and their colleagues showed that antibodies targeted to CD276 extended survival in a mouse brain metastasis model. The researchers also highlighted the utility of their integrated cross-species platform for the identification of additional therapeutic targets in the vasculature of brain metastases.
Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms
Cancer Cell, 2024 January 18