Immunotherapy of uveal melanoma

Uveal melanoma is a malignancy with exceptional features for treatment with immunotherapy. Primary uveal melanoma can be treated with a variety of therapies that may limit the growth of the primary tumor in the eye and partially preserve vision. However, none of these treatment modalities prevents the development of metastases, which predominantly arise in the liver and universally remain fatal. Novel therapies are being explored for their effectiveness against uveal melanoma metastases and immunotherapy may be a potential option as an alternative or adjunctive treatment, even in the prophylactic setting. Uveal melanoma may be particularly responsive to T-cell-based immunotherapy because it originates in the immune-privileged eye. The localization of the primary tumor in the immune-privileged eye excuses the tumor cells from continuous immunological pressure. This may render primary uveal melanoma more immunogenic than tumor cells from non-privileged sites and allow expression of novel tumor antigens to which the patient's endogenous T cell repertoire is not tolerized. The clinical and genetic differences between cutaneous and uveal melanomas underscore the need for immunotherapy specifically designed for uveal melanoma patients. In this review, the current developments in the field of immunotherapy for uveal melanoma are discussed, with a special emphasis on T-cell-based strategies.