Implication de la voie Notch et des cellules lymphoïdes innées lors d’un hépatocarcinome cellulaire

Responsable de l’encadrement : Pr Rachel Golub et Dr. Isabelle Damei

Tél : 01 45 68 87 66 Fax : 01 45 68 84 21 E-mail:

Institut Pasteur

Résumé du Projet de Stage

Notch is a signaling pathway involved in the development of solid tumors via the induction of tumoral Notch receptor ligand expression. It also conditions development and functions of lymphoid subsets. Innate lymphoid cells (ILC) are immune partners involved in cancer immune surveillance. Type 1 ILC comprises NK cells and ILC1 that could use the Notch-related program to secrete anti-tumoral molecules. NK cells are known to be crucial to control the tumor progression and their resident liver ILC1 counterpart were not studied in that context. Type 1 ILC are downregulated in hepatocellular carcinoma (HCC) and could not fight the tumoral progression. We propose to uncover the mechanisms downregulating the NK/ILC1 response against HCC. We aim to understand how these cells are repressed and whether the notch pathway could modulate their polarization and functions. We already observed that activating these cells had tremendous effect on stopping the early tumor growth. We propose to evaluate whether activation via IL15 stimulations on top of specific anticheckpoints antibodies could enhance their direct antitumoral activities and/or modulate the immune response of their specific T cell partners: CD8 T cells and Treg. Acting on pro-tumoral TGFβ+ Treg is important since TGFβ is a strong HCC contributor and also a suppressive NK/CD8 T cell agent. Notch positively modulates TGFβ, Treg numbers and functions in the tumor microenvironment. Some HCC therapeutic strategies proposed tools inhibiting the Notch pathway highlighting the importance of understanding the Notch biology on the immune environment.

 Dernières Publications en lien avec le projet :

1. Bourayou, E. & Golub, R. Signaling Pathways Tuning Innate Lymphoid Cell Response to Hepatocellular Carcinoma. Front. Immunol. 13, 846923 (2022).
2. Perchet T, Petit M, Banchi EG, Meunier S, Cumano A, Golub R (2018) The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions. Front Immunol. 9:1252.
3. Xu W, Cherrier D, Chea S, Vosshenrich C, Serafini N, Petit M, Liu P, Golub R, Di Santo J (2019) A novel Id2RFP reporter mouse strain redefines ILC precursor potentials. Immunity
4. Chea S, Perchet T, Petit M, Verrier T, Guy-Grand D, Banchi EG, Vosshenrich CAJ, Di Santo JP, Cumano A. & Golub R (2016) Notch signaling in group 3 ILC modulates their plasticity. Sci Signal. 9(426):ra45.
5. Ishizuka IE*, Chea S*, Gudjonson H, Constantinides MG, Dinner AR, Bendelac A & Golub R (2016) Single cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue–inducer cell lineage. Nat Immunol. 17(3):269-76.

Ce projet s’inscrit dans la perspective d’une thèse

 Ecole Doctorale de rattachement : BioSPC


Intitulé de l’Unité : Lymphocytes et Immunité
Nom du Responsable de l’Unité : Pr Ana Cumano
Nom du Responsable de l’Équipe : : Pr Rachel Golub
Adresse : Institut Pasteur, 25 Rue du docteur Roux, 75015 Paris