Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2024; 15(1): 23-31
Published online Jan 24, 2024. doi: 10.5306/wjco.v15.i1.23
Uveal melanoma: Recent advances in immunotherapy
Francesco Saverio Sorrentino, Francesco De Rosa, Patrick Di Terlizzi, Giacomo Toneatto, Andrea Gabai, Lucia Finocchio, Carlo Salati, Leopoldo Spadea, Marco Zeppieri
Francesco Saverio Sorrentino, Patrick Di Terlizzi, Department of Surgical Sciences, Unit of Ophthalmology, Ospedale Maggiore, Bologna 40100, Italy
Francesco De Rosa, Department of Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”, Meldola 47014, Italy
Giacomo Toneatto, Andrea Gabai, Lucia Finocchio, Carlo Salati, Marco Zeppieri, Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
Leopoldo Spadea, Eye Clinic, Policlinico Umberto I, “Sapienza” University of Rome, Rome 00142, Italy
Author contributions: De Rosa F and Zeppieri M wrote the outline; De Rosa F assisted in the revisions of the manuscript; Salati C and Spadea L assisted in the editing of the manuscript; Zeppieri M assisted in the conception and design of the study, and completed the English and scientific editing (a native English speaking MD, PhD); Sorrentino FS, De Rosa F, Di Terlizzi P, Toneatto G, Gabai A, Finocchio L, Salati C, Spadea L, and Zeppieri M participated in the manuscript writing; Sorrentino FS, De Rosa F, Di Terlizzi P, Toneatto G, and Gabai A contributed to the research; Sorrentino FS and Zeppieri M provided the final approval of the version of the article.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Marco Zeppieri, BSc, MD, PhD, Doctor, Department of Ophthalmology, University Hospital of Udine, p.le S. Maria della Misericordia 15, Udine 33100, Italy.
Received: November 1, 2023
Peer-review started: November 1, 2023
First decision: November 29, 2023
Revised: December 7, 2023
Accepted: January 2, 2024
Article in press: January 2, 2024
Published online: January 24, 2024

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM’s distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

Keywords: Uveal melanoma, Immunotherapy, Ocular oncology, Tumor, Metastatic disease, Genetic mutations

Core Tip: Our minireview will cover the latest studies about immunotherapy for uveal melanoma (UM) metastatic disease. Driver genes and oncogenic mutations have been largely investigated. Up to half of affected patients develop metastases that are the leading single cause of death after diagnosis of UM. Precise systemic therapy addressing metastatic UM and significantly improving the surveillance is not available for each single case. However, identifying predictive factors, achieving international consensus on surveillance protocols, aiming to inactivate micrometastases, and standardizing outcomes would be crucial to be able to effectively cure metastatic UM.