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

Figure 1 Mechanisms of resistance to immunotherapy in melanoma and corresponding therapeutic strategies. Schematic representation of the main biological pathways involved in immune resistance, including defects in antigen presentation, cytokine-mediated immunosuppression, and adaptive upregulation of inhibitory checkpoints. The right panel highlights therapeutic strategies currently under investigation to overcome these barriers, such as interferon-γ priming, epigenetic modulation, dual checkpoint blockade, and transforming growth factor-β inhibition. MHC-I: Major histocompatibility complex class I; B2M: Β2-microglobulin; JAK: Janus kinase; STAT: Signal transducer and activator of transcription; IFN-γ: Interferon-γ; LAG-3: Lymphocyte-activation gene 3; TIM-3: T-cell immunoglobulin and mucin domain-containing protein 3; TIGIT: T cell immunoreceptor with Ig and ITIM domains; TGF-β: Transforming growth factor-β; IL-10: Interleukin-10; MDSCs: Myeloid-derived suppressor cells; TAMs: Tumor-associated macrophages; HDACI: Histone deacetylase inhibitors; DNMTI: DNA methyltransferase inhibitors; VEGF: Vascular endothelial growth factor.