May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
PD-L1 Expression by Human Uveal Melanoma Inhibits T-Cell Function
Author Affiliations & Notes
  • W. Yang
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • P. W. Chen
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • H. Li
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • H. Alizadeh
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • J. Y. Niederkorn
    Ophthalmology, UT Southwestern Medical Center at Dallas, Dallas, Texas
  • Footnotes
    Commercial Relationships  W. Yang, None; P.W. Chen, None; H. Li, None; H. Alizadeh, None; J.Y. Niederkorn, None.
  • Footnotes
    Support  NIH grants EY05631, CA30276 and an unrestricted grant from Research to Prevent Blindness, Inc., New York, NY.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2398. doi:https://doi.org/
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    • Get Citation

      W. Yang, P. W. Chen, H. Li, H. Alizadeh, J. Y. Niederkorn; PD-L1 Expression by Human Uveal Melanoma Inhibits T-Cell Function. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2398. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Tumors employ a variety of strategies to evade immune surveillance. The costimulatory molecule PD-L1 which binds to its receptor PD-1 expressed on T-cells plays an inhibitory role in the regulation of T cell activation and function. The purpose of this study is to test the hypothesis that PD-L1 expression by uveal melanoma promotes tumor immune escape from T cell-mediated killing by inhibiting T cell function.

Methods: : A panel of primary and metastatic uveal melanoma cell lines was evaluated for PD-L1 expression by RT-PCR and FACS analysis respectively. Uveal melanoma-bearing eyes were detected for PD-L1 expression in situ by immunohistochemistry. PD-L1 function was tested by co-culturing IFN-γ -pretreated uveal melanoma cells with activated Jurkat T cells for 48 hours and assessing IL-2 production of T cell by ELISA.

Results: : Six primary uveal melanoma cell lines and two metastases cell lines constitutively expressed PD-L1 mRNA, while five of the nine primary and one of the five metastatic uveal melanoma cell lines tested constitutively expressed PD-L1 protein at various levels, which indicates a posttranscriptional control of PD-L1 surface expression. However, all primary and metastatic uveal melanoma cell lines upregulated PD-L1 expression significantly after stimulation with IFN-γ (P<0.01). Immunhistochemistry demonstrated that PD-L1 was not expressed by uveal melanoma in situ. IL-2 production by activated Jurkat cells was decreased significantly when the cells co-cultured with IFN-γ pretreated uveal melanoma cells (P<0.01). IL-2 production was restored to over 70% by addition of anti-PD-L1 or anti- PD-1 antibody into the co-culture 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-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 of uveal melanomas.

Keywords: melanoma • immunomodulation/immunoregulation • oncology 
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