Functions and clinical implications of the liver microenvironment in hepatic uveal melanoma metastases

Uveal melanoma (UM) is an aggressive intraocular malignancy in adults arising from the melanocytes of the uveal tract. While primary UM lesions can be successfully treated, ~ 50% of UM patients develop metastases primarily in the liver. Patients with liver metastatic UM (LMUM) have poor prognosis and few therapeutic options. LMUM lesions are unresponsive to standard chemotherapies, targeted therapies, and immune checkpoint inhibitors — an effect at least in part associated with the detoxification function of the liver and the diverse hepatic immunological landscape. Here, we recount the etiology and molecular mechanisms in the development of LMUM, examine the influences of the hepatic tumor microenvironment (TME) on UM liver tropism, and review how the innate and peripheral immune response contributes to LMUM progression and therapeutic efficacy. The unique immunological properties of the liver coupled with the distinct growth patterns of LMUM lesions present significant challenges for developing effective treatments that can overcome this specialized microenvironment. Improved understanding of the interplay between the liver and LMUM is essential for the development of more effective diagnostic techniques and improved therapeutic outcomes.