Programmed cell death ligand-1 expression in tumor and immune cells is associated with better patient outcome and decreased tumor-infiltrating lymphocytes in uveal melanoma

• Published in: Modern pathology 2018-08, Vol.31 (8), p.1201-1210
• Main Authors: Zoroquiain, Pablo, Esposito, Evangelina, Logan, Patrick, Aldrees, Sultan, Dias, Ana Beatriz, Mansure, Jose Joao, Santapau, Daniela, Garcia, Ciro, Saornil, Maria Antonia, Belfort Neto, Rubens, Burnier, Miguel N.
• Format: Article
• Language: English
• Subjects: 13/1; 13/106; 13/109; 14/63; 38/109; 38/77; 42/89; 692/53/2422; 692/53/2423; 82/51; 82/80; Adult; Aged; Antigen-presenting cells; Apoptosis; B7-H1 Antigen - biosynthesis; Biomarkers, Tumor - analysis; Cell death; Clinical trials; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Laboratory Medicine; Ligands; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Male; Medicine; Medicine & Public Health; Melanoma; Melanoma - immunology; Melanoma - mortality; Melanoma - pathology; Metastases; Metastasis; Middle Aged; Multivariate analysis; Pathology; Patients; PD-1 protein; PD-L1 protein; Prognosis; T cell receptors; Therapeutic applications; Tumor cells; Tumor-infiltrating lymphocytes; Uveal Neoplasms - immunology; Uveal Neoplasms - mortality; Uveal Neoplasms - pathology
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-018-0043-5

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.