Le vendredi 17 octobre, Madame Cléa DZIAGWA, titulaire d'un Master sciences, technologies, santé mention cancer, parcours type biologie du cancer (Université de Lyon I) et d'un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Monsieur Pierre CLOSE.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "A new role of t6A tRNA modification in melanoma immune response". 

Le jury sera composé de :

Alain CHARIOT (Président), Francesca RAPINO (Secrétaire), Marco BINDER (German Cancer Res.), Pierre CLOSE, Christophe DESMET, Eleonora LEUCCI (KUL), Mitch LEVESQUE (Univ. Zurich), Thomas MARICHAL, Laurent NGUYEN.

Résumé de la thèse

Stimulating the immune system to launch an anti-tumor response holds great potential for cancer treatment. Melanoma, the most aggressive form of skin cancer, has continued to rise in both incidence and mortality over the past 40 years. Fortunately, recent scientific breakthroughs have transformed therapeutic approaches for melanoma patients. In our lab, we uncovered a crucial link between specific changes in molecules called tRNAs and melanoma’s ability to resist targeted treatments (Rapino et al., Nature 2018). These tRNA modifications influence how proteins are produced in cancer cells, and our study focuses on understanding how these changes impact the immune system’s response to melanoma. To explore this, we conducted an unbiased analysis of more than 50 enzymes that modify tRNAs, examining their roles in maintaining protein stability and regulating the immune response to tumors. One specific modification site on tRNA, known as position 37, emerged as critical for protein integrity. However, we found that protein instability alone does not necessarily trigger an anti-tumor response. When we tested these findings in mice, we discovered that the catalytic subunit of the KEOPS complex, called OSGEP, plays a pivotal role in activating strong anti-tumor immunity. Reducing OSGEP levels slowed melanoma tumor growth and extended tumor-free survival, primarily through the activation of T cells. Further investigations revealed that the loss of OSGEP activates RIG-I, an important RNA sensor necessary for T cell activation and tumor control. This positions OSGEP as a key regulator of the immune response against melanoma, offering a promising target for new cancer therapies.