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.
背景：葡萄膜黑色素瘤（UM）患者在初次诊断数年后发生转移，通常预示着不良预后。关于参与此过程的细胞性质目前尚存争议。血液中发现的兼具肿瘤细胞与免疫细胞特征的循环杂交细胞可预测转移发生，并可能与原发肿瘤中的双特性细胞（DNC）相对应。本研究旨在确定原发UM肿瘤中DNC的存在情况、参与其生成的细胞类型及其体外形成能力。方法：对38例UM病灶采用HMB45联合免疫细胞特异性抗体进行免疫标记。同时，通过共培养UM细胞与外周血单个核细胞（PBMCs）以分析DNC的形成过程。结果：90%（26/29）的肿瘤中存在HMB45+/CD45+ DNCs，93%（26/28）存在HMB45+/CD8+ DNCs，71%（17/24）存在HMB45+/CD68+ DNCs。与CD8+和CD68+细胞形成的DNCs分别与其对应免疫细胞的浸润程度呈正相关。值得注意的是，UM细胞在体外易与PBMCs形成杂交细胞。结论：本研究对UM中DNC的表型特征分析表明，CD8+ T细胞和巨噬细胞具有形成DNC的能力，这对深入理解肿瘤转移扩散机制具有重要意义，从而为开发新型治疗途径奠定基础。
The Phenotypical Characterization of Dual-Nature Hybrid Cells in Uveal Melanoma
肿瘤(癌症)患者之家