Nathalie Vigneron

Major achievements

• Discovery of the key role played by the proteasome in the production of spliced antigenic peptides recognized by cytolytic T lymphocytes.
• Identification of a number of novel antigenic peptides recognized by cytolytic T lymphocytes on tumor. 

Question

• Which antigenic peptides, recognized by anti-tumor cytolytic T lymphocytes are the optimal targets for cancer immunotherapy?
• What role do the different proteasome subtypes play within cells and in shaping the antigenic peptide repertoire?
• How to induce an efficient anti-tumor response to tumors affected in their antigen processing pathway?

Research focus

Cancer cells have been shown to exhibit "markers," known as tumor antigens, which flag cancer cells for recognition by the immune system. Tumor antigens consist in small peptides of 8 to 10 amino acids, presented at the cell surface by class I molecules of the Major Histocompatibility Complex (MHC). These peptides result from the breakdown of cellular proteins by a large protease called the proteasome. At the cell surface, tumor antigens are recognized by a specific population of white blood cells called the cytolytic T lymphocytes, which can recognize and kill tumor cells. Novel anti-cancer therapeutic approaches, known as « cancer immunotherapy » aim at activating these T cells so that they can help patients destroy their tumor. However, many patients still fail to respond to such therapies, likely because they lack an appropriate anti-tumor response. There is therefore an urgent need to develop cancer vaccines or adoptive T-cell therapies efficiently targeting tumor antigens, in order to improve anti-tumor responses in patients. Our work aims at identifying such antigens, which would be optimal targets for cancer immunotherapy. To do so, we study how tumor antigens are produced within tumors and in particular, how the different proteasome subtypes influence the nature of the antigenic peptide repertoire. Although loss of the components of the MHC class I processing pathway often affects the antigenic peptide repertoire and generally favors cancer immune evasion, it sometimes also unveil new tumor antigens, which we are actively trying to characterize, as they might represent interesting targets for cancer immunotherapy.

Nathalie Vigneron obtained her Master’s degree in biological sciences from the University of Liège (Belgium) in 1999. She then joined the lab of Dr. Benoit Van den Eynde at UCLouvain (Belgium), where she obtained her PhD in Biomedical Sciences in 2005, working on the identification of antigenic peptides produced by peptide splicing in the proteasome. After her PhD thesis, she completed a postdoctoral training in the group of Pr. Peter Cresswell at Yale University (USA), where she studied the role of various components of the MHC class I presentation pathway on the establishment of the antigenic peptide repertoire. After this three year post-doctoral training, Nathalie returned to the de Duve institute, where she continued her researches on the processing of antigenic peptides, setting up together with Vincent Stroobant the analysis of the MHC class I-associated peptide repertoire by mass spectrometry. Nathalie officially became a Group leader in 2023. She is also an invited lecturer at the UCLouvain since 2022.

Honors

• Fonds Joseph Maisin in 2014, 2018 and 2022
• Médaille du Prix Alvarenga de Piauhy à l’Académie royale de médecine de Belgique (2010)
• Marie Curie Outgoing International Fellowship (2006 – 2008)
• D. Collen Research Foundation Fellow, Belgian American Educational Foundation (2005).

Affiliations

• Group leader, de Duve Institute, Brussels
• Chargée de cours invitée, UCLouvain
• Investigator, Ludwig Cancer Research, Brussels