Combination Immunotherapy for Mucosal Melanoma: Molecular Mechanism, Research Status, and Future Directions

Mucosal melanoma is a rare and aggressive subtype of melanoma, accounting for 1%-2% of new cases in the United States in 2023, and 20%-30% in China and other Asian countries. Its origin is often occult, with the lack of early clinical features, the absence of actionable driver mutations, and poor response to immunotherapy, all contributing to its poor prognosis. The rarity of this subtype leads to limited awareness and interventions. Furthermore, due to its immune evasion mechanisms, mucosal melanoma shows resistance to traditional immune checkpoint inhibitors. Consequently, new therapeutic strategies are urgently needed to improve patient outcomes. Recent clinical trials have suggested that combination immunotherapy can overcome immune evasion, reduce resistance to treatment, produce synergistic anti-tumor effects, and improve survival. Epidemiological factors and clinical characteristics play significant roles in diagnosis and prognosis, while the mutational landscape influences responses to immunotherapy. This review provides an overview of these aspects and systematically discusses current research on combination therapies and emerging immunotherapy approaches for mucosal melanoma. It also explores potential future directions for treatment, aiming to enhance therapeutic strategies for this rare cancer and improve patient outcomes.