Collaborations
Ulf KLEIN, Leeds University, UK
Stephane DALLE, Hôpitaux Lyon-Sud et CRCL, France
Gilles MARODON, CIMI, Paris, France
Christophe CAUX, CRCL, Lyon, France
Benoit SALOMON, CIMI, Paris, France
Julie CARAMEL, CRCL, France
Grants
Programme Atip-Avenir
Labex DEVweCAN
Fondation ARC
Fondation BMS
Fondation ARSEP
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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.
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.
Grinberg-Bleyer Y, Caron R, Seeley JJ, De Silva NS, Schindler CW, Hayden MS, Klein U, Ghosh S. “The Alternative NF-κB Pathway in Regulatory T Cell Homeostasis and Suppressive Function.” J Immunol. 2018 Apr 1;200(7):2362-2371.
Grinberg-Bleyer Y., Oh H., Desrichard A., Bhatt D.M., Caron R., Chan T.A., Schmid R., Hayden M.S., Klein U., and Ghosh S. “NF-kB c-Rel is crucial for the regulatory T cell immune checkpoint in cancer.” Cell, 2017 Sep 7;170(6):1096-1108
Oh H.*, Grinberg-Bleyer Y.*, Liao W., Maloney D., Wang P., Wu Z., Wang J., Bhatt D.M., Heise N., Schmid R., Hayden M.S., Klein U., Rabadan R. and Ghosh S. (* Equal contribution) “An NF-kB-dependent, lineage specific transcriptional program regulates Treg identity and function.” Immunity, 2017 Sep 19;47(3):450-465
Grinberg-Bleyer Y, Ghosh S. “A novel link between inflammation and cancer.” Cancer Cell, 2016 Dec 12; 30(6):829. Review.
Grinberg-Bleyer Y, Dainichi T, Oh H, Heise N, Klein U, Schmid RM, Hayden MS, Ghosh S. “Cutting edge: NF-κB p65 and c-Rel control epidermal development and immune homeostasis in the skin. ” J Immunol. 2015 Mar 15;194(6):2472
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