Laboratoire
Equipe d’Accueil : Cancer and Immuen response/ Cancer Immunotherapy and Cell Reprogramming
Intitulé de l’Unité : Institut Cochin
Nom du Responsable de l’Unité : F. Niedergang
Nom du Responsable de l’Équipe : E. Donnadieu / N. Bercovici & A. Prevost-Blondel
Adresse : 27 rue du Faubourg Saint Jacques, 75014 Paris
Responsable de l’encadrement : N. Bercovici
Tel : +33 6 80 52 79 46 mail : nadege.bercovici@inserm.fr
Résumé du projet de Stage :
Metastases are the leading cause of cancer-related death. In contrast to conventional therapies, immunotherapies have taken an unexpected step forward in improving patient survival, suggesting that boosting the immune system can induce a long-term protection in responding patients to prevent the development of metastases. While preclinical research investigating immunotherapy has classically focused on primary tumors, only a few studies have explored the mechanisms controlling metastases.
Recent advances have underlined that immunotherapies induce a drastic remodeling of the tumor microenvironment. In particular, our group showed in various mouse models that myeloid cells, in particular macrophages and monocytes, are activated after immunotherapy and closely cooperate with tumor-infiltrating T lymphocytes for the regression of primary tumors (Bercovici et al., 2019; Thoreau et al., 2015; Weiss et al., 2017) and to prevent local tumor relapse (Guérin et al., 2020). Based on these results, we hypothesised that the immunotherapy-induced modification of immune cells (in particular myeloid cells and T cells), may also impact metastatic outbreak. In the 4T1 breast tumor model, in which metastases frequently develop in the lungs after spreading from the primary tumor, our preliminary data showed that a STING agonist not only induced the regression of the primary tumor but also decreased the metastatic load. Combining in vitro and in vivo approaches with spectral cytometry, fluorescence microscopy and transcriptomics analyses, the M2 project will aim at deciphering the immunotherapy-induced modifications of the immune system that may antagonize different steps of the metastatic process.
Dernières Publications en lien avec le projet :
1. Vermare A, Guérin MV, Peranzoni E, Bercovici N. 2022. Dynamic CD8+ T Cell Cooperation with Macrophages and Monocytes for Successful Cancer Immunotherapy. Cancers. Jul 21;14(14):3546. doi: 10.3390/cancers14143546.
2. Guerin MV, Regnier F, Thoreau M, Vimeux L, Benard M, Dransart E, Penny HL, Johannes L, Trautmann A, Bercovici N. 2020. Local IFNα enhances the anti-tumoral efficacy of systemic anti-PD1 to prevent tumor relapse. 2020. J Immunother Cancer. Nov;8(2):e000996. doi: 10.1136/jitc-2020-000996.
3. Guerin, M.V., V. Finisguerra, B.J. Van den Eynde, N. Bercovici, and A. Trautmann. 2020. Preclinical murine tumor models: a structural and functional perspective. Elife. 9. doi:10.7554/eLife.50740.
4. Guerin MV, Regnier F, Feuillet V, Vimeux L, Weiss JM, Bismuth G, Altan-Bonnet G, Guilbert T, Thoreau M, Finisguerra V, Donnadieu E, Trautmann A, Bercovici N. 2019. TGFβ blocks IFNα/β release and tumor rejection in spontaneous mammary tumors. Nat Commun. 2019 Sep 11;10(1):4131. doi: 10.1038/s41467-019-11998-w.PMID:
3151151
Ce projet s’inscrit dans la perspective d’une thèse avec financement par concours de l’ED BioSPC