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Pablo Zoroquiain, Ana Beatriz Toledo Dias, Patrick Logan, Sultan Aldrees, Evangelina Esposito, Miguel N Burnier; Programmed cell death ligand 1 expression in uveal melanoma is associated with better patient outcome. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5893.
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© ARVO (1962-2015); The Authors (2016-present)
Programmed cell death-1/ligand (PD1/PD-L1) is a co-inhibitor pathway that negatively regulates T-cell activity. PD-L1 expression in tumors has been associated with responders to PD1/PD-L1 inhibitor treatments. Despite advances in uveal melanoma (UM) treatment, 40% of patients will develop liver metastases and the vast majority will succumb to their disease. The aim of this study was to analyze PD-L1 as a prognostic marker and as a possible therapeutic target for UM.
A total of 77 enucleated eyes from UM patients with pertinent clinical information, including survival rate and metastasis-free period, were analyzed. Histopathological criteria, such as cell type and lymphocytic infiltration, were also evaluated. Histological sections of placenta and the 92.1 UM cell line were used as a positive controlto validate the anti-PD-L1 antibody (E1L3N clone). Negative controls were established by silencing the PD-L1 gene with siRNA in the 92.1 UM cell line. For each UM eye, retinal pigment epithelium or corneal epithelium staining were used as internal controls (positive). Greater than 5% membranous staining threshold defined PD-L1 positivity as established in clinical trials for non-ocular tumors.The Chi-square test and survival analysis using log-rank test were used to determine statistical significance.
Antibody validation showed a significant decrease in immunohistochemical expression (P<0.0001) after gene silencing (9-fold decrease in PD-L1 mRNA). Of the 77 cases, 8 UM eyes were excluded due to absence of internal positive control staining. Of the 69 remaining cases, median age was 65 years (range:31-89) and median follow up time was 36 months(range: 2-155). PD-L1 expression was seen in 59.4% of the cases. PD-L1 expression was associated with a longer metastasis free period (P=0.01) and overall survival (P=0.04). No differences in PD-L1 expression were seen according to UM cell type, lymphocytic infiltrate, size, macrophage infiltrate, or location.
PD-L1 is expressed in uveal melanoma in a similar proportion compared with other cancers and is associated with better outcome. These results support the evaluation of anti-PD1/PD-L1 pathway therapy in UM. Pre-clinical trials are needed to elucidate the importance of this marker in UM for predicting response to treatments targeting this pathway.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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