The Phenotypical Characterization of Dual-Nature Hybrid Cells in Uveal Melanoma.

Simple Summary: Uveal melanoma (UM) is a rare type of cancer of the eye that develops from a cell type called melanocytes, which are present in the uveal tract. These patients have a high risk of liver metastasis, usually many years after the initial diagnosis, which is life threatening. We discovered a population of cells in the primary tumor called dual-nature hybrid cells (DNCs) similar to previously discovered cells in the blood (i.e., circulating hybrid cells, CHCs) with shared characteristics of both cancer cells and white blood cells. In this paper, we determined the types of white blood cells capable of participating in the formation of a hybrid cell with a cancer cell, and we re-created these DNCs in a cell culture. The study of the cells of this tumor, particularly DNCs, is crucial to better understanding dissemination and uncovering a possible target for treatment of this systemic disease. Background: Metastasis, occurring years after primary diagnosis, represents a poor prognosis in uveal melanoma (UM)-affected individuals. The nature of cells involved in this process is under debate. Circulating hybrid cells that have combined tumor and immune cell features found in blood were predictive of metastasis and may correspond to dual-nature cells (DNC) in the primary tumor. Herein, we sought to determine the presence of DNCs in primary UM tumors, the cell types involved in their genesis, and their ability to be formed in vitro. Methods: UM lesions (n = 38) were immunolabeled with HMB45 in combination with immune-cell-specific antibodies. In parallel, we co-cultured UM cells and peripheral blood mononuclear cells (PBMCs) to analyze DNC formation. Results: HMB45+/CD45+ DNCs were present in 90% (26/29) of the tumors, HMB45+/CD8+ DNCs were present in 93% (26/28), and HMB45+/CD68+ DNCs were present in 71% (17/24). DNCs formed with CD8+ and CD68+ cells were positively correlated to the infiltration of their respective immune cells. Notably, UM cells were prone to hybridize with PBMCs in vitro. Conclusions: This phenotypical characterization of DNCs in UM demonstrates that CD8+ T-cells and macrophages are capable of DNC formation, and they are important for better understanding metastatic dissemination, thus paving the path towards novel therapeutic avenues. [ABSTRACT FROM AUTHOR]