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

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.

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.

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.

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.