| Autor: |
Zhengpeng Wan, Shun Zhang, Amy X. Zhong, Liling Xu, Mark F. Coughlin, Georgios Pavlou, Sarah E. Shelton, Huu Tuan Nguyen, Satomi Hirose, Seunggyu Kim, Marie A. Floryan, David A. Barbie, F. Stephen Hodi, Roger D. Kamm |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Advanced Science, Vol 11, Iss 26, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202400921 |
| Popis: |
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 αVβ3. Overall, this study provides a new biophysical explanation for high PD‐L1 expression in tumoral vasculatures. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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