Dissection of tumor and immune heterogeneity of MiT family translocation renal cell carcinomas in mice and human

• Applicant: Dr. Nassim Tawanaie Pour Sedehi
• Subject Area: Reproductive Medicine, Urology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 510961958

Translocation (t)RCC is a heterogeneous group of tumours that develop due to translocations involving the TFEB or TFE3 transcription factors. The nature of the fusion protein generated by translocation is associated with different histopathological features and patient outcomes. Tumour microenvironment (TME) can impact patient outcome and treatment response, especially to immune checkpoint inhibitors. Preliminary studies show that in tRCC, TME composition appears associated with the nature of the fusion protein. However, how fusion proteins influence TME composition, treatment response and patient outcome remains unknown. To address this, we generated novel mouse models directing inducible expression of NONO-TFE3, ASPSCR1-TFE3 as well as native TFE3 or TFEB in the kidney epithelium. I will evaluate tumour initiation and development and their clinico-pathological features. Furthermore, I will assess the impact of the different fusion proteins on gene expression and TME composition and correlate the mouse data with the transcriptomes and TMEs of human tRCC. We aim to exploit the murine models to define novel molecular and immune targets pertinent to precision medicine for human tRCC.

• DFG Programme: WBP Fellowship
• International Connection: France
• Host: Professor Dr. Gabriel Malouf