Immune landscape of melanoma: Tumor microenvironment, resistance mechanisms, and predictive biomarkers

Melanoma, a highly immunogenic malignancy, has become a paradigm for immune-based therapies. Despite remarkable responses to immune checkpoint inhibitors, many patients exhibit primary or acquired resistance. These outcomes are largely driven by the composition and dynamics of the tumor microenvironment, which shape immune activation, suppression, and therapeutic responsiveness, contributing to immune escape. Moreover, checkpoint molecule expression, altered antigen presentation, and immunosuppressive cytokine profiles further hinder effective immune surveillance. Advances in biomarker discovery have provided valuable insights into predicting therapy response and guiding individualized treatment. This review discusses the interplay between melanoma and its immune microenvironment, explores mechanisms of immune resistance, and highlights emerging predictive biomarkers with potential to refine clinical decision-making and improve outcomes.