The role of altered blood vessels in brain tumors

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 (Image: Pixabay CC0)
(Image: Pixabay CC0)

In a recent research, scientists have revealed new insights into the complex network of blood vessels in brain metastases, which were not well understood before. They’ve emphasized a significant increase in a molecule called CD276, known for its role in immune regulation. What’s promising is that experimental antibodies targeting CD276 have shown positive results in early trials, suggesting a potential breakthrough in treatment approaches.

The research, conducted by Leire Bejarano and Johanna Joyce from the Lausanne Branch of the Ludwig Institute for Cancer Research, is published in Cancer Cell. The study sheds light on crucial aspects of brain metastasis and aims to unravel the intricacies of blood vessel structures within brain tumors, with the hope of revolutionizing treatment strategies.

Scientists delved into the detailed network of blood vessels in human brain metastases, particularly those originating from aggressive tumors like lung, melanoma, and breast cancers. Using advanced techniques such as single-cell and bulk RNA-sequencing, they carefully examined the key components of blood vessels, specifically endothelial and mural cells.

The thorough analysis not only identified various subtypes of blood vessels enriched in brain metastases but also uncovered immune regulatory subtypes not recognized before. By combining human data with information from mouse models of brain metastases, they established a strong preclinical foundation for identifying potential treatment targets within blood vessels. Notably, the study revealed a significant increase in the CD276 immune checkpoint molecule in the blood vessels of both human and mouse brain metastases. Early trials with antibodies blocking CD276 showed promising results, representing a significant step forward in designing innovative therapeutic interventions. These findings greatly contribute to our understanding of the complex interactions between blood vessels, immune cells, and cancer cells in the context of brain metastases.

The collaboration involved the Department of Neurosurgery, the Department of Oncology, the Department of Pathology, and the Neuroscience Research Center at the Centre Hospitalier Universitaire Vaudois (CHUV) and the Swiss Institute of Bioinformatics (SIB). Dr. Bejarano’s work in the Joyce lab also acknowledges postdoctoral fellowships from the European Molecular Biology Organization and the Human Frontier Science Program.

Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms, Leire Bejarano et al., in Cancer Cell, Open Access, Published: January 18, 2024, DOI:­/j.ccell.2­023.12.018