Purchase this article with an account.
Aysegul Tura, Anna Kraus, Mahdy Ranjbar, Julia Lueke, Salvatore Grisanti; Expression of the programmed cell death ligand 1 (PD-L1) on uveal melanoma cells with Monosomy-3. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3967.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The programmed cell death ligand 1 (PD-L1) is a glycoprotein, which is upregulated on most tumor cells. PD-L1 can promote immune escape via binding to the PD-1 receptor on lymphocytes and rendering the T cells unresponsive to tumor cells. The expression of PD-L1 can be induced by various proinflammatory molecules, with interferon(IFN)-gamma being the most potent inducer. In this study, we analyzed the extent of IFN-gamma dependent PD-L1 upregulation in uveal melanoma (UM) cells with regard to the presence of monosomy-3. We also examined the efficacy of the dietary flavonoid quercetin in suppressing the PD-L1 upregulation.
UM cells were isolated from the primary tumor of a patient (female, 39 years) operated in our clinic, who developed liver metastases within 2 years after enucleation. Cultured cells (Passages 1-3) were dissociated by dispase, seeded on to 8-well chamber slides, and incubated in culture medium (RPMI-1640 supplemented with 10% fetal bovine serum, 2 mM L-Glutamine and penicillin/streptomycin) with or without IFN-gamma (25 ng/ml) and Quercetin (100 µM) for 2 days. An Immuno-FISH assay was developed for the simultaneous detection of the PD-L1 protein and chromosome-3.
Monosomy-3 was detected in a minimum of 60% of the cultured cells. Control cells incubated in normal culture medium exhibited a weak PD-L1 expression on the cell surface. IFN-gamma led to a significant but uneven upregulation in PD-L1 expression, with some cells exhibiting a particularly high level of this protein. Immuno-FISH assays demonstrated a higher degree of IFN-gamma-dependent PD-L1 upregulation on most cells with Monosomy-3 compared to the cells with Disomy-3. Quercetin could significantly suppress the IFN-gamma dependent PD-L1 upregulation on UM cells.
The higher level of PD-L1 upregulation in the UM cells with Monosomy-3 might be one of the mechanisms underlying the elevated metastatic potential of these cells. Treatment with the dietary flavonoid quercetin can be considered as a novel therapy option to prevent the escape of these cells from the immune system.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only