Published online Jan 24, 2024. doi: 10.5306/wjco.v15.i1.23
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
Processing time: 82 Days and 7.5 Hours
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.
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.