葡萄膜黑色素瘤（UM）是一种罕见但致命的肿瘤。它以其高转移潜力而闻名，使其成为最具侵略性和致命性的癌症之一。最近，免疫检查点，如程序性细胞死亡蛋白-1（PD1）和细胞毒性T淋巴细胞相关蛋白-4（CTLA-4），在多种人类癌症中显著提高患者生存率，尤其是皮肤黑素瘤。然而，由于分子特征往往与皮肤黑素瘤大相径庭，葡萄膜黑素瘤患者被排除在这些研究之外。本研究旨在分析V domain Ig抑制T细胞激活（VISTA）作为一种新型免疫检查点的表达情况，评估其预后意义以及与PD1和CTLA-4之间的相关性。通过TCGA数据库分析和两个独立队列的免疫组化检测，进行了VISTA、CTLA-4和PD1表达的评估。我们的结果显示，VISTA的表达与肿瘤的侵袭性、T细胞衰竭以及患者的最短中位总生存期相关。令人惊讶的是，所有患者的PD1蛋白表达均为阴性，而CTLA-4的表达在晚期患者中较高。我们的发现表明，VISTA可能是葡萄膜黑素瘤患者的一种预后标志物和免疫治疗的吸引人策略。探索其表达谱可以预测免疫治疗的反应，并可能促进恶性葡萄膜黑素瘤患者的精准治疗改进。版权所有©2023 Issam Salah, Marnissi, Lakhdar, Karkouri, ElBelhadji和Badou。

Uveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4.Evaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM.Our results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients.Copyright © 2023 Issam Salah, Marnissi, Lakhdar, Karkouri, ElBelhadji and Badou.