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Wanhua Yang, Peter W. Chen, Haochuan Li, Hassan Alizadeh, Jerry Y. Niederkorn; PD-L1: PD-1 Interaction Contributes to the Functional Suppression of T-Cell Responses to Human Uveal Melanoma Cells In Vitro. Invest. Ophthalmol. Vis. Sci. 2008;49(6):2518-2525. doi: 10.1167/iovs.07-1606.
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purpose. To assess the expression of PD-L1 on human uveal melanomas and its potential to suppress T-cell function.
methods. A panel of primary and metastatic uveal melanoma cell lines was evaluated for PD-L1 expression by RT-PCR and flow cytometric analysis. Uveal melanoma-containing eyes were examined for PD-L1 expression by immunohistochemistry. PD-L1 function was tested by coculturing IFN-γ-pretreated uveal melanoma cells with activated Jurkat T cells for 48 hours and assessing T-cell production of IL-2 by ELISA.
results. Five of the nine primary and one of the five metastatic uveal melanoma cell lines tested constitutively expressed PD-L1 protein at various levels. However, all primary and metastatic uveal melanoma cell lines upregulated PD-L1 expression after stimulation with IFN-γ. Immunohistochemistry demonstrated that PD-L1 was not expressed by primary uveal melanomas in situ. IL-2 production by activated Jurkat T cells was decreased significantly when the cells were cocultured with IFN-γ-pretreated uveal melanoma cells. More than 70% of IL-2 production was restored by addition of either anti-PD-L1 or anti-PD-1 antibody to the coculture assays (P < 0.01).
conclusions. Expression of PD-L1 by uveal melanoma cells regulates T-cell function by suppressing IL-2 production. The results imply that the presence of IFN-γ in the tumor local microenvironment promotes upregulation of PD-L1 expression by uveal melanoma, which may, in part, promote immune escape by impairing T-cell function. The selective blockade of PD-L1 is a potential strategy in T-cell-based immunotherapy for uveal melanoma.
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