Human endogenous retroviruses (hERVs) are stably integrated in the human genome and are significantly expressed in clear cell renal cell carcinoma (ccRCC), the most frequent kidney malignancy. As hERV expression in human cancers has been identified by many studies, they are thought to contribute to malignant transformation. On the other hand, reactivation of transcription of hERV genes can activate a strong immune response against the tumor. Recently, ccRCC samples from patients responsive to anti-PD-1 therapy were shown to have high expression of certain hERVs, suggesting a role of hERVs in the modulation of the tumor immune microenvironment. In this project, I am interested to study the role of hERVs in ccRCC, focusing on their dynamics and spatial heterogeneity during disease progression and therapy response. This research will greatly contribute to expand our knowledge on the role of hERVs in ccRCC, their regulation and effect on the tumor microenvironment and immunotherapy.