Programmed cell death-1/ligand (PD-1/PD-L1) interaction negatively regulates T cell activity. PD-L1 expression in tumor cells, antigen-presenting cells, and lymphocytes of the tumor microenvironment is associated with response to treatment with PD-1/PD-L1 inhibitors, but there is still debate on the cutoff value that correlates with responders. In uveal melanoma (UM), 40% of patients will develop liver metastases and, amongst them, 90% will succumb to their disease. The aim of this study was to analyze PD-L1 expression as a prognostic marker and as a possible therapeutic target for UM. Sixty-seven enucleated eyes from UM patients with relevant clinical information were analyzed. Univariate and multivariate analysis were used to evaluate association of PD-L1 with survival. PD-L1 expression was positive relatively to tumor cells, immune cells, and the tumor and tumor-infiltrating immune cell group scoring in 46, 34 and 55% of the cases, respectively. On univariate analysis, tumor cells and the tumor and tumor-infiltrating immune cell group PD-L1 expression was associated with a longer metastasis-free survival (P = 0.04 and P = 0.007). However, on multivariate analysis, only the tumor and tumor-infiltrating immune cell group positivity was associated with longer metastasis-free survival (P = 0.01). Furthermore, tumor cells and the tumor and tumor-infiltrating immune cell group PD-L1 expression was associated with decreased tumor-infiltrating lymphocytes (P = 0.02). PD-L1, when expressed in uveal melanoma, is associated with better patient outcome and decreased tumor-infiltrating lymphocytes. These results support the consideration of anti-PD-1/PD-L1 therapy in uveal melanoma. To determine the best cutoff value, further studies from patients enrolled in clinical trials treated with PD-1/PD-L1 inhibitors are necessary.
The majority of patients who underwent diode laser therapy for threshold ROP had favorable anatomical and visual outcomes. However, high refractive error and strabismus may be clinically the pertinent causes of visual impairment.
The relatively high rate of dysplasia in a low ultraviolet light index area challenges the main cause of this disease in our population, a hypothesis that should be evaluated in future studies. We suggest that all PT samples should be sent for histopathological evaluation even in areas with low ultraviolet light index.
BackgroundLight exposure and more specifically the spectrum of blue light contribute to the oxidative stress in Age-related macular degeneration (AMD). The purpose of the study was to establish whether blue light filtering could modify proangiogenic signaling produced by retinal pigmented epithelial (RPE) cells under different conditions simulating risk factors for AMD.MethodsThree experiments were carried out in order to expose ARPE-19 cells to white light for 48 h with and without blue light-blocking filters (BLF) in different conditions. In each experiment one group was exposed to light with no BLF protection, a second group was exposed to light with BLF protection, and a control group was not exposed to light. The ARPE-19 cells used in each experiment prior to light exposure were cultured for 24 h as follows: Experiment 1) Normoxia, Experiment 2) Hypoxia, and Experiment 3) Lutein supplemented media in normoxia. The media of all groups was harvested after light exposure for sandwich ELISA-based assays to quantify 10 pro-angiogenic cytokines.ResultsA significant decrease in angiogenin secretion levels and a significant increase in bFGF were observed following light exposure, compared to dark conditions, in both normoxia and hypoxia conditions. With the addition of a blue light-blocking filter in normoxia, a significant increase in angiogenin levels was observed. Although statistical significance was not achieved, blue light filters reduce light-induced secretion of bFGF and VEGF to near normal levels. This trend is also observed when ARPE-19 cells are grown under hypoxic conditions and when pre-treated with lutein prior to exposure to experimental conditions.ConclusionsFollowing light exposure, there is a decrease in angiogenin secretion by ARPE-19 cells, which was abrogated with a blue light - blocking filter. Our findings support the position that blue light filtering affects the secretion of angiogenic factors by retinal pigmented epithelial cells under normoxic, hypoxic, and lutein-pretreated conditions in a similar manner.
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