Department of Dermatology, Universitätsklinikum Erlangen, Friedrich Alexander University, Ulmenweg 18, 91054 Erlangen, Germany.
Department of Dermatology and Allergy, University Hospital, LMU Munich, Frauenlobstr. 9-11, 80337 Munich, Germany.
Int J Mol Sci. 2020 Jan 29;21(3):879. doi: 10.3390/ijms21030879.
Uveal melanoma (UM) represents the most common intraocular malignancy in adults and accounts for about 5% of all melanomas. Primary disease can be effectively controlled by several local therapy options, but UM has a high potential for metastatic spread, especially to the liver. Despite its clinical and genetic heterogeneity, therapy of metastatic UM has largely been adopted from cutaneous melanoma (CM) with discouraging results until now. The introduction of antibodies targeting CTLA-4 and PD-1 for immune checkpoint blockade (ICB) has revolutionized the field of cancer therapy and has achieved pioneering results in metastatic CM. Thus, expectations were high that patients with metastatic UM would also benefit from these new therapy options. This review provides a comprehensive and up-to-date overview on the role of ICB in UM. We give a summary of UM biology, its clinical features, and how it differs from CM. The results of several studies that have been investigating ICB in metastatic UM are presented. We discuss possible reasons for the lack of efficacy of ICB in UM compared to CM, highlight the pitfalls of ICB in this cancer entity, and explain why other immune-modulating therapies could still be an option for future UM therapies.
葡萄膜黑色素瘤 (UM) 是成年人中最常见的眼内恶性肿瘤，约占所有黑色素瘤的 5%。几种局部治疗选择可以有效控制原发性疾病，但 UM 具有很高的转移扩散潜力，特别是转移到肝脏。尽管存在临床和遗传异质性，但转移性 UM 的治疗在很大程度上沿用了皮肤黑色素瘤 (CM) 的方法，迄今为止结果并不理想。针对 CTLA-4 和 PD-1 的抗体用于免疫检查点阻断 (ICB) 的引入彻底改变了癌症治疗领域，并在转移性 CM 中取得了开创性的结果。因此，人们期望转移性 UM 患者也能从这些新的治疗选择中获益。这篇综述全面而详尽地介绍了 ICB 在 UM 中的作用。我们总结了 UM 的生物学特性、临床特征以及与 CM 的区别。介绍了几项研究在转移性 UM 中研究 ICB 的结果。我们讨论了与 CM 相比，ICB 在 UM 中缺乏疗效的可能原因，强调了 ICB 在这种癌症实体中的陷阱，并解释了为什么其他免疫调节疗法仍然是未来 UM 治疗的一种选择。
