Immunobiology of uveal melanoma

Uveal melanoma is the most common malignant intraocular tumor in adults. The malignancy of uveal melanoma is correlated with its capacity to metastasize to distant organs. Indeed, liver metastasis remains the leading cause of death in uveal melanoma patients. Although primary uveal melanomas can be effectively treated with surgery or radiotherapy, there is no known therapeutic modality with proven efficacy in prolonging life or ameliorating liver metastases. Sadly, the 5-year mortality rate for uveal melanoma patients has not changed in the past 30 years. Although uveal melanoma cells express tumor-specific antigens that can elicit immune responses, the tumors escape immune elimination due to the sanctuary provided by the immune privilege of the eye. Once uveal melanoma cells metastasize to the liver, they enter an immunologically hostile environment. However, mounting evidence suggests that uveal melanoma cells adopt many of the properties and mechanisms that contribute to immune privilege in the eye and thereby create ad hoc immune privilege at the metastatic site. Although uveal melanomas have multiple immune escape mechanisms, new insights into the nature of immune privilege offer glimmers of hope for the development of novel and effective immunotherapeutic strategies for treating this blinding and deadly neoplasm.