Immune Phenotyping for Patient Stratification in NRAS-Mutant Melanoma

Melanoma is one of the most common skin cancers worldwide. Among its molecular subtypes, NRAS-mutant melanoma is associated with a more aggressive clinical course and poorer prognosis than other forms of the disease. Although the immune system plays a fundamental role in the recognition and elimination of melanoma cells, tumor progression is frequently accompanied by immune evasion mechanisms, including the establishment of an immunosuppressive microenvironment and the upregulation of immune checkpoint pathways. While immune checkpoint inhibitors have significantly improved the treatment of melanoma, their long- term efficacy may be limited by resistance mechanisms and treatment- related toxicities. Therefore, the characterization of circulating immune cell populations may provide valuable information on systemic immune alterations potentially associated with disease progression and therapeutic response. The aim of this thesis was to characterize the peripheral immune profile of patients affected by metastatic NRAS-mutant melanoma (CET ANV 2024-45) through flow cytometric analysis of peripheral blood mononuclear cells (PBMCs), with a particular focus on T-lymphocyte and regulatory T cell subsets and selected immune checkpoint molecules.