PD-L1: PD-1 Interaction Contributes to the Functional Suppression of T Cell Responses to Human Uveal Melanoma Cells In Vitro
Wanhua Yang 1,
Peter W. Chen 1,
Haochuan Li 1,
Hassan Alizadeh 1,
and
Jerry Y. Niederkorn 2*
1 Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States
2 Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390-9057, United States
* To whom correspondence should be addressed. E-mail: jerry.niederkorn{at}utsouthwestern.edu.
 |
Abstract |
|---|
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-
-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-. Immunhistochemistry demonstrated that PD-L1 was not expressed by uveal melanomas in situ. IL-2 production by activated Jurkat T cells was decreased significantly when the cells were cocultured with IFN--pretreated uveal melanoma cells. IL-2 production was restored to over 70% by addition of either anti-PD-L1 or anti- PD-1 antibody into the coculture assays (P<0.01).
Conclusions: Expression of PD-L1 by uveal melanoma cells regulates T cell function by suppressing IL-2 production. This study implies that the presence of IFN- 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 of uveal melanomas.
Key Words:
melanoma, immunoregulation, immune privilege, cytokine
