Molecular regulation of cancer immunity

Objectives

Cancer progression is often indexed to the quality of the anti-tumor immune response. Conversely, these immune responses can be deleterious in the settings of autoimmune diseases. In this context, understanding the molecular mechanisms orchestrating the function of immune cells in their target tissues, is of major interest for the development of new therapies for cancer and autoimmunity. The team “Molecular Regulation of Cancer Immunity” is particularly interested in the role of the NF-kB family of transcription factors in T-cell biology. Our recent work has demonstrated specific and divergent functions of the different NF-kB subunits in the function of regulatory T cells, which are potent inhibitors of immunity. Our goal now is to decipher the possible roles of NF-kB in the function of effector T cells (Teff), which have dual functions: protective in cancer and pathogenic in autoimmune diseases. Our work may not only reveal new mechanisms of regulation of the immune system, but also highlight new therapeutic targets for the treatment of cancer or autoimmunity.

Projects

The research of the team is articulated around 3 major projects:

• The characterization of NF-kB subunits in the basal Teff biology.
• The study of NF-kB functions in cancer progression and response to immunotherapies.
• The study of the impact of NF-kB in the pathogenic functions of Teff in autoimmune diseases.

This research is based on a common methodology in 3 axes:

• The use of unique pre-clinical mouse models.
• The use of patient samples and the ablation of NF-kB in vitro in human cells
• High-throughput sequencing (RNA-seq, CHIP-Seq, ATAC-Seq) to understand NF-kB functions at the whole genome level.