Abstract
Purpose :
The aim of this study was to analyze PD-L1 as a prognostic marker and as a possible therapeutic target for UM.
Methods :
67 enucleated eyes from UM patients with relevant clinical information were analyzed. Immunostaining was performed with an anti-PD-L1 E1L3N clone and retinal pigment epithelium as an internal positive control. PD-L1 knockdown in the 92.1 cell line was used as a negative control. Two types of PD-L1 expression were analyzed: the conventional method: >5% membranous staining in tumor cells; and an alternative method: >5% in either tumor cells or non-tumor cells (TNT). Cases were evaluated by 2 ocular pathologists and using an image analyzer. Univariate and multivariate analysis were used to evaluate PDL1 association with survival, and the kappa score was calculated to compare agreement between manual and automated evaluation.
Results :
PD-L1 expression was positive by tumor cell and TNT counts in 46.3% and 55.2% of the cases, respectively. On univariate analysis, tumor cell and TNT PD-L1 expression were associated with a longer metastasis free survival (MFS; P<0.05). However, on multivariate analysis, only TNT positivity was associated with longer MFS (P=0.01). Furthermore, tumoral and TNT PD-L1 expression was associated with decreased tumor infiltrating lymphocytes (TIL, P=0.02). Automated evaluation of TNT showed good agreement with the pathologist evaluation (κ=0.764) and correlated with longer MFS after both univariate and multivariate analysis (P<0.05).
Conclusions :
PD-L1 is expressed in UM and is associated with better outcome and decreased TIL. These results support the evaluation of anti-PD1/PD-L1 therapy in UM. Automated analysis showed good correlation with conventional methods. Due to its higher objectivity and reproducibility, it is a promising tool that can be utilized in designating a cutoff value for future clinical trials.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.