Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms.
Cancer Cell
; 42(3): 378-395.e10, 2024 Mar 11.
Article
de En
| MEDLINE
| ID: mdl-38242126
ABSTRACT
Brain metastasis (BrM) is a common malignancy, predominantly originating from lung, melanoma, and breast cancers. The vasculature is a key component of the BrM tumor microenvironment with critical roles in regulating metastatic seeding and progression. However, the heterogeneity of the major BrM vascular components, namely endothelial and mural cells, is still poorly understood. We perform single-cell and bulk RNA-sequencing of sorted vascular cell types and detect multiple subtypes enriched specifically in BrM compared to non-tumor brain, including previously unrecognized immune regulatory subtypes. We integrate the human data with mouse models, creating a platform to interrogate vascular targets for the treatment of BrM. We find that the CD276 immune checkpoint molecule is significantly upregulated in the BrM vasculature, and anti-CD276 blocking antibodies prolonged survival in preclinical trials. This study provides important insights into the complex interactions between the vasculature, immune cells, and cancer cells, with translational relevance for designing therapeutic interventions.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du cerveau
/
Tumeurs du sein
/
Mélanome
Limites:
Animals
/
Female
/
Humans
Langue:
En
Journal:
Cancer Cell
Sujet du journal:
NEOPLASIAS
Année:
2024
Type de document:
Article