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Clear cell renal cell carcinoma (ccRCC) is characterized by the inactivation of the Von Hippel-Lindau (VHL) tumour suppressor gene, leading to the stabilization and accumulation of hypoxia-inducible factor 2α (HIF2α) and constitutive activation of hypoxia-inducible pathways. This thesis aimed to investigate the role of HIF2α as a central driver of tumour progression, immune evasion and metabolic adaptation in ccRCC.