Uveal melanoma exhibits marked resistance to immunotherapy with response rates below 15%, driven by an immunologically "cold" tumor microenvironment characterized by low T-cell infiltration and abundant immunosuppressive cell populations.
Tebentafusp, the first FDA-approved treatment for metastatic uveal melanoma, demonstrates sustained survival benefits with a 27% three-year survival rate compared to 18% in control groups, representing a significant therapeutic breakthrough.
Novel combination strategies targeting multiple resistance mechanisms simultaneously show promise, including dual checkpoint blockade, epigenetic modulators, and metabolic pathway inhibitors that can overcome the tumor's complex immune evasion strategies.
Emerging predictive biomarkers, including BAP1 mutations, MBD4 deficiency, and circulating tumor DNA levels, are enabling personalized treatment approaches and improving patient selection for immunotherapy regimens.
