LALLE Guilhem
Engineer
(from September/October 2018)
PONCET Clara
Master 2 Student
(from Septembre/October 2018)
DUC Capucine
Master 2 Student
(from September/october 2018)
Collaborations
Ulf KLEIN, Leeds University, UK.
Stephane DALLE, Hôpitaux Lyon-Sud et CRCL, France.
Gilles MARODON, CIMI, Paris, France.
Christophe CAUX, CRCL, Lyon, France.
Pierre SAINTIGNY, CRCL, Lyon, France.
Grants
Labex DEVweCAN
|
Cancer progression is often indexed to the quality of the anti-tumor immune response. In this context, understanding of the molecular mechanisms orchestrating immune cells function in the tumor microenvironment is of major interest for the development of new cancer therapies. Our team "Molecular Regulation of Cancer Immunity" is particularly interested in the role of the NF-kB family of transcription factors in T-cell biology in cancer. 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 anti-tumor immunity. Our goal is now to decipher the possible roles of NF-kB in the function of effector T cells, which have a protective function in cancer. Our work could not only reveal new mechanisms of regulation of the immune system, but also highlight new therapeutic targets for the treatment of cancer.
We have created unique tools to dissect the discrete functions of NF-kB subunits in T-cell biology and cancer progression.
 -In a first axis, we study the impact of NF-kB ablation in mouse T-cell subsets, on their function during cancer growth and in the response to checkpoint-blockade therapies.
-Our second project is dedicated to the study of NF-kB in human T-cell subsets through the use of samples from both patients with melanoma and healthy donors.
-Finally we wish to setup a large-scale comprehensive analysis of the molecular regulation of immune responses by NF-kB. We use high-throughput sequencing approaches (RNA-Seq, ChIP-Seq and ATAC-Seq) to create a unifying model of the regulation of gene expression in cancer immunity.
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
|