In order to understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with or without the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients.
Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. Hazard ratios and their 95% confidence intervals (CI) were noted for each parameter and independent prognostic factors were identified by univariate and multivariate analysis through Cox proportional-hazards models.
Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p=0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p=0.03). DFS rate were lower in patients with TILs with positive immunoreactivity and mRNA expression of PD-1 and PD-L1 but the rate of DFS was seen significantly better in patients with expression of PD-L1 in patients without TILs.
To conclude, TILs play an important immune cell for achieving successful immunotherapeutic strategies in the treatment of UM patients. Our finding suggests that PD-1 and PD-L1 expression in TILs showed poor outcome that helps in identifying a subgroup of UM patients who may benefit from immunotherapy.
Legal entity responsible for the study
All authors have declared no conflicts of interest.