Laboratory of Research on Neurologic, Neurosensorial Diseases and Handicap, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
Immuno-Genetics and Human Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
Front Immunol. 2023 Aug 18;14:1225140. doi: 10.3389/fimmu.2023.1225140. eCollection 2023.
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.
葡萄膜黑色素瘤（UM）是一种罕见但致命的肿瘤。它以高转移性为特征，是最具侵袭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了患者的生存率，尤其是皮肤黑色素瘤。然而，UM 患者被排除在这些研究之外，因为它们的分子特征往往与皮肤黑色素瘤有很大的不同。本研究旨在分析 V 域免疫球蛋白抑制性 T 细胞激活物（VISTA）的表达，这是一种新的免疫检查点，评估其预后意义及其与 PD1 和 CTLA-4 的相关性。
通过 TCGA 数据库分析和用原发性恶性 UM 进行的两种独立队列的免疫组化来评估 VISTA、CTLA-4 和 PD1 的表达。
我们的结果表明，VISTA 的表达与肿瘤侵袭性、T 细胞耗竭以及患者的中位总生存期最短有关。令人惊讶的是，所有患者的 PD1 蛋白表达均为阴性，而晚期患者的 CTLA-4 表达较高。我们的研究结果表明，VISTA 可能是 UM 患者免疫治疗的预后标志物和有吸引力的治疗策略。探索其表达谱可能预测对免疫治疗的反应，并可能导致恶性葡萄膜黑色素瘤患者的精准治疗得到改善。
