Unlocking Mysteries of Brain Tumors: New Study Reveals Secrets of Altered Blood Vessels.
This new research unveils the previously poorly understood heterogeneity of the brain metastasis vasculature, highlighting the significant upregulation of the CD276 immune checkpoint regulator. Notably, anti-CD276 antibodies show promising results in preclinical trials, revealing a potential advance in treatment strategies.
The study*, published in Cancer Cell, was conducted by Dr Leire Bejarano and colleagues and directed by Prof. Johanna Joyce, member of the Lausanne Branch of the Ludwig Institute for Cancer Research. This new research sheds light on critical aspects of brain metastasis and aims to unravel the complexities of the vasculature within brain tumors, potentially revolutionizing therapeutic strategies.
The researchers explore the intricate vascular landscape of human brain metastasis (BrM). As they grapple with the challenges posed by aggressive tumors, particularly those stemming from lung, melanoma, and breast cancers, they investigate the hitherto poorly understood heterogeneity within the BrM microenvironment. Employing cutting-edge techniques such as single-cell and bulk RNA-sequencing, they meticulously examine the major vascular components, specifically endothelial and mural cells.
This comprehensive analysis not only identifies multiple BrM-enriched vascular subtypes but also reveals previously unrecognized immune regulatory subtypes. Integrating their human data with datasets they generated in parallel from various BrM mouse models, they establish a robust preclinical platform for pinpointing potential therapeutic targets within the vasculature. Notably, the study unveils a significant upregulation of the CD276 immune checkpoint molecule in the BrM vasculature of both human and mouse. Preclinical trials with anti-CD276 blocking antibodies revealed promising results, offering a significant advance in designing innovative therapeutic interventions. The findings thus contribute substantially to the understanding of the complex interplay between vasculature, immune cells, and cancer cells in the context of brain metastasis.
* Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms
This work is the result of a collaboration between the Department of Neurosurgery, the Department of Oncology, the Department of Pathology and Neuroscience Research center at the Centre Hospitalier Universitaire Vaudois (CHUV) and the Swiss Institute of Bioinformatics (SIB). Research in the Joyce lab for this study was supported in part by the Swiss National Science Foundation Advanced Grant Award, Ludwig Institute for Cancer Research, University of Lausanne, Carigest Foundation, Breast Cancer Research Foundation, and the Lundin Brain Tumor Center to Prof. Joyce. Dr. Bejarano additionally acknowledges postdoctoral fellowships she received from European Molecular Biology Organisation and Human Frontier Science Program.
by Carine Dournes Söhnlein (DO communication UNIL-CHUV)