葡萄膜黑色素瘤（UM）是成人最常见的眼内肿瘤，一旦发生转移，预后很差，因为转移性疾病的治疗方案无效。在过去的十年中，基于免疫疗法的新型癌症疗法已经改变了不同形式癌症的治疗格局，带来了改善患者总生存期（OS）的许多希望。 VISTA、LAG-3 和 PRAME 是免疫治疗的新靶标，最近在不同实体瘤中引起了关注，但其在 UM 中的相关性至今仍有待全面评估。在这里，我们使用免疫组织化学方法研究了来自单个中心（法国尼斯尼斯大学医院）的 30 名原发性 UM 病例的代表性全组织切片中 VISTA、LAG-3 和 PRAME 的蛋白表达。这些标记物的表达均与不同的临床和病理参数相关，包括转移的发生和 OS。我们证明了 VISTA 和 LAG-3 在浸润肿瘤的小淋巴细胞中表达，而在 UM 细胞中未检测到这些蛋白的表达。对于 PRAME，在 UM 细胞中观察到核表达，但在肿瘤浸润免疫细胞中未发现表达。肿瘤浸润淋巴细胞 (TIL) 中 VISTA 表达水平的升高与核 BAP1 表达和更好的预后相关。 TIL 中较高水平的 LAG-3 与较高水平的 CD8 阳性 TIL 相关。黑色素瘤细胞中的 PRAME 核阳性与上皮样细胞占优势 (>90%) UM 组织学亚型、较高的有丝分裂数和较高的染色体 8q 增益百分比相关。这项研究提出 VISTA 作为原发性 UM 中的一种新型相关免疫检查点分子，并有助于确认 LAG-3 和 PRAME 作为治疗 UM 患者的潜在重要免疫治疗靶点，有助于扩大与调节相关的免疫治疗候选分子的数量。这种侵袭性癌症。版权所有 © 2023 作者。由 Elsevier B.V. 出版。保留所有权利。

Uveal melanoma (UM) is the most common intraocular tumour in adults, with dismal prognosis once metastases develop, since therapeutic options for the metastatic disease are ineffective. Over the past decade, novel cancer therapies based on immunotherapy have changed the landscape of treatment of different forms of cancer leading to many hopes of improvement in patient overall survival (OS). VISTA, LAG-3 and PRAME are novel promising targets of immunotherapy that have recently gained attention in different solid tumours, but whose relevance in UM remained to be comprehensively evaluated until now. Here, we studied the protein expression of VISTA, LAG-3 and PRAME using immunohistochemistry in representative whole tissue sections from primary UM cases in a cohort of 30 patients from a single centre (Nice University Hospital, Nice, France). The expression of each of these markers was correlated with different clinical and pathological parameters, including onset of metastases and OS. We demonstrated the protein expression of VISTA and LAG-3 in small lymphocytes infiltrating the tumour, while no expression of the proteins was detected in UM cells. For PRAME, nuclear expression was observed in UM cells, but no expression in tumour infiltrating immune cells was identified. Increased levels of VISTA expression in tumour infiltrating lymphocytes (TILs) were associated with nuclear BAP1 expression and better prognosis. Higher levels of LAG-3 in TILs were associated with higher levels of CD8-positive TILs. PRAME nuclear positivity in melanoma cells was associated with epithelioid cell dominant (>90%) UM histological subtype, higher mitotic numbers and a higher percentage of chromosome 8q gain. This study proposes VISTA as a novel relevant immune checkpoint molecule in primary UM and contributes to confirm LAG-3 and PRAME as potentially important immunotherapy targets in the treatment of UM patients, helping to expand the number of immunotherapy candidate molecules that are relevant to modulate in this aggressive cancer.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.