Immunoregulation and Biotherapy (I-BIOT)
Topic
Our team works on the modulation of the immune response applied to allografts (including gestation) and cancer. Our conceptual contributions rely on original discoveries in the field of checkpoints of the immune response (IL4I1, TNFR2, TFH interaction – B cells). We also take a fresh look at the interactions between immune response and tumor microenvironment by studying the interdependencies between tumor vascular normalization and quality of the immune response with or without therapeutic intervention.
We have several experimental models in the field of grafts (skin, HSC) in immunocompetent or immunodeficient mice. We have strong expertise in surgery, anatomopathology, immunohistochemistry, flow cytometry, 3D imaging (in collaboration with the Vision Institute), ultrasound of small animals and on tumor analysis (human or mouse) in close collaboration with locally-pathology and oncology departments (digital pathology, patient monitoring).
We are also developing tumor organoids from cell lines or directly from patient biopsies, in order to limit animal testing while expanding our field of investigation.
Our interactions are close with nephrology, clinical hematology, medical oncology, radiotherapy and obstetrics gynecology departments and we host a large part of their translational research activities.
We lead the clinical investigation center in biotherapy (J Cohen/P Grimbert), which we use as a platform for the development of early phase clinical trials based on our research. We also coordinate the “Fédération hospital-universitaire” FHU “TRUE, Innovative therapy for immune disorders” (PI Philippe Grimbert) and the “Focis center of excellence” in transplantation and cancer (PI José Cohen).
We coordinate a mass spectrometry platform set up and managed by José Courty, CNRS research director. Damien Habert, UPEC assistant engineer, is in charge of its operation/development and we have welcomed Sandrine Bourgoin, MCF at the UGA and expert in this technology for the past two years within the framework of a collaboration agreement with the UPEC. This platform is located on the central campus and is open to all IMRB teams. contact: jose.courty@u-pec.fr
Our team also hosts Biopredic International, (Ismael Ben Mosbah, Manager and Fatiha Mahtout, Laboratory technician). Biopredic’s expertise relates to the isolation, production and distribution of human and animal biologics, including tissues, primary cells, cell lines and reagents.
Expected benefits and Valuation
Our goal is to develop new therapeutic tools based on an in-depth knowledge in the fields of transplantation and cancer, two target fields of pathologies of dysfunctions of the immune response. Our recent work has led to several invention patents, some of which are licensed. We have also many interactions with private companies through the development of clinical trials or new biotherapy tool development.
Selected publications
Castellano F, Prevost-Blondel A, Cohen JL, Molinier-Frenkel V. What role for AHR activation in IL4I1-mediated immunosuppression ?
Oncoimmunology. 2021 May 12;10(1)):1924500. doi: 10.1080/2162402X.2021.1924500.PMID: 34026337Raineri F, Bourgoin-Voillard S, Cossutta M, Habert D, Ponzo M, Houppe C, Vallée B, Boniotto M, Chalabi-Dchar M, Bouvet P, Couvelard A, Cros J, Debesset A, Cohen JL, Courty J, Cascone I. Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma.
Cancers (Basel). 2021 Jun 15;13(12):2986. doi: 10.3390/cancers13122986.PMID: 34203710Nicolas-Boluda A, Vaquero J, Vimeux L, Guilbert T, Barrin S, Kantari-Mimoun C, Ponzo M, Renault G, Deptula P, Pogoda K, Bucki R, Cascone I, Courty J, Fouassier L, Gazeau F, Donnadieu E. Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment.
Elife. 2021 Jun 9;10:e58688. doi: 10.7554/eLife.58688.PMID: 34106045Ferrara B, Belbekhouche S, Habert D, Houppe C, Vallée B, Bourgoin-Voillard S, Cohen JL, Cascone I, Courty J. Cell surface nucleolin as active bait for nanomedicine in cancer therapy: a promising option.
Nanotechnology. 2021 May 17;32(32). doi: 10.1088/1361-6528/abfb30.PMID: 33892482 Review.Joher N, Matignon M, Grimbert P. HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers.
Front Immunol. 2021 May 20;12:688301. doi: 10.3389/fimmu.2021.688301. eCollection 2021.PMID: 34093594Moktefi A, Hivelin M, Grimbert P, Carmagnat M, Sbidian E, Papouin B, Suberbielle C, Wolkenstein P, Bosc R, Meningaud JP, Lantieri L, Ortonne N. Face transplantation: A longitudinal histological study focusing on chronic active and mucosal rejection in a series with long-term follow-up.
Am J Transplant. 2021 Jan 14. doi: 10.1111/ajt.16489. Online ahead of print.PMID: 33445219Puiffe ML, Dupont A, Sako N, Gatineau J, Cohen JL, Mestivier D, Lebon A, Prévost-Blondel A, Castellano F, Molinier-Frenkel V. IL4I1 Accelerates the Expansion of Effector CD8+ T Cells at the Expense of Memory Precursors by Increasing the Threshold of T-Cell Activation.
Front Immunol. 2020 Dec 4;11:600012. doi: 10.3389/fimmu.2020.600012. eCollection 2020.PMID: 33343572Castellano F, Molinier-Frenkel V. Control of T-Cell Activation and Signaling by Amino-Acid Catabolizing Enzymes.
Front Cell Dev Biol. 2020 Dec 17;8:613416. doi: 10.3389/fcell.2020.613416. eCollection 2020.PMID: 33392202Darche M, Cossutta M, Caruana L, Houppe C, Gilles ME, Habert D, Guilloneau X, Vignaud L, Paques M, Courty J, Cascone I. Antagonist of nucleolin, N6L, inhibits neovascularization in mouse models of retinopathies.
FASEB J. 2020 Apr;34(4):5851-5862. doi: 10.1096/fj.201901876R. Epub 2020 Mar 5.PMID: 32141122Presset M, Djordjevic D, Dupont A, Le Gall E, Molinier-Frenkel V, Castellano F. Identification of inhibitors of the immunosuppressive enzyme IL4I1.
Bioorg Chem. 2020 Jan;94:103463. doi: 10.1016/j.bioorg.2019.103463. Epub 2019 Nov 23.PMID: 31812258Naserian S, Abdelgawad ME, Afshar Bakshloo M, Ha G, Arouche N, Cohen JL, Salomon BL, Uzan G. The TNF/TNFR2 signaling pathway is a key regulatory factor in endothelial progenitor cell immunosuppressive effect. Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease.
Cell Commun Signal. 2020 Jun 16;18(1):94. doi: 10.1186/s12964-020-00564-3.PMID: 32546175Boucault L, Lopez Robles MD, Thiolat A, Bézie S, Schmueck-Henneresse M, Braudeau C, Vimond N, Freuchet A, Autrusseau E, Charlotte F, Redjoul R, Beckerich F, Leclerc M, Piaggio E, Josien R, Volk HD, Maury S, Cohen JL, Anegon I, Guillonneau C. Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease.
Blood Adv. 2020 Jun 9;4(11):2501-2515. doi: 10.1182/bloodadvances.2020001688.PMID: 32511714Pilon C, Bigot J, Grondin C, Thiolat A, Lang P, Cohen JL, Grimbert P, Matignon M. Phenotypic and Transcriptomic Lymphocytes Changes in Allograft Recipients After Intravenous Immunoglobulin Therapy in Kidney Transplant Recipients.
Front Immunol. 2020 Jan 24;11:34. doi: 10.3389/fimmu.2020.00034. eCollection 2020.PMID: 32038663Pilon C, Stehlé T, Beldi-Ferchiou A, Matignon M, Thiolat A, Burlion A, Grondin C, Birebent B, Pirenne F, Rouard H, Lang P, Marodon G, Grimbert P, Cohen JL. Human Apoptotic Cells, Generated by Extracorporeal Photopheresis, Modulate Allogeneic Immune Response.
Front Immunol. 2019 Dec 18;10:2908. doi: 10.3389/fimmu.2019.02908. eCollection 2019.PMID: 31921167Lantieri L, Cholley B, Lemogne C, Guillemain R, Ortonne N, Grimbert P, Thervet E, Lellouch AG. First human facial retransplantation: 30-month follow-up.
Lancet. 2020 Nov 28;396(10264):1758-1765. doi: 10.1016/S0140-6736(20)32438-7.PMID: 33248497
Documentation
The team
Composition
- Responsable : José Cohen
- Responsable délégué (e) : Ilaria Cascone
- Chercheur : Mélissande Cossutta, José Courty
- Enseignant-Chercheur : Daniel Azoulay, Asma Beldi-Ferchiou, Yazid Belkacemi, Ilaria Cascone, Flavia Castellano, José Cohen, Philippe Grimbert, Bassam Haddad, Edouard Lecarpentier, Mathieu Leclerc, Sébastien Maury, Valérie Molinier-Frenkel, Allan Thiolat, Christophe Tournigand
- Praticien hospitalier : Rim Cherif, Marie Matignon
- Post doctorant : Benedetta Ferrara, Sahar Kassem, Sylvain Meunier
- Doctorant : Orianne Bonizec, Anaïs Debesset, Jérôme Gatineau, Matteo Ponzo, Fabio Raineri, Fidj Sandre, Nhu-Hanh To
- Ingénieur : Aurélie Dupont, Damien Habert, Caroline Pilon, Marie-Line Puiffe, Audrey Ridoux, Benoît Vallée
- Technicien : Claire Justine-Houppe
- Gestionnaire : Eric Scoazec
- Stagiaire : Karim El-Sakhawi, Flavie Tholozan
IMRB – Inserm U955
Immunorégulation et Biothérapie (I-BIOT) – Equipe José Cohen
Bâtiment R – Rez-de-chaussée
Hôpital Henri Mondor
51, avenue du Maréchal De Lattre de Tassigny
94010 Créteil
Contact
Tél. : 01 49 81 43 91
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