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Transmural Flow Upregulates PD-L1 Expression in Microvascular Networks
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DOI：10.1002/advs.202400921.png)
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Abstract
En 中文
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 alpha(V)beta(3). Overall, this study provides a new biophysical explanation for high PD-L1 expression in tumoral vasculatures.
Keywords:
integrin alpha(V)beta(3)
microfluidic
microvasculature
PD-L1
tumor microenvironment
transmural flow
Journal
IF:
14.1
Papers:
1.7W
Citations:
11.5W