Transmural Flow Upregulates PD-L1 Expression in Microvascular Networks.
Adv Sci (Weinh)
; 11(26): e2400921, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38696611
ABSTRACT
Endothelial programmed death-ligand 1 (PD-L1) expression is higher in tumors than in normal tissues. Also, tumoral vasculatures tend to be leakier than normal vessels leading to a higher trans-endothelial or transmural fluid flow. However, it is not clear whether such elevated transmural flow can control endothelial PD-L1 expression. Here, a new microfluidic device is developed to investigate the relationship between transmural flow and PD-L1 expression in microvascular networks (MVNs). After treating the MVNs with transmural flow for 24 h, the expression of PD-L1 in endothelial cells is upregulated. Additionally, CD8 T cell activation by phytohemagglutinin (PHA) is suppressed when cultured in the MVNs pre-conditioned with transmural flow. Moreover, transmural flow is able to further increase PD-L1 expression in the vessels formed in the tumor microenvironment. Finally, by utilizing blocking antibodies and knock-out assays, it is found that transmural flow-driven PD-L1 upregulation is controlled by integrin αVß3. Overall, this study provides a new biophysical explanation for high PD-L1 expression in tumoral vasculatures.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Cima
/
Microvasos
/
Antígeno B7-H1
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Adv Sci (Weinh)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos