Laetitia Dubouchet, Helena Todorov, Ruth Seurinck, Nicolas Vallet, Sofie Van Gassen, Aurélien Corneau, Catherine Blanc, Habib Zouali, Anne Boland, Jean-François Deleuze, Brian Ingram, Regis Peffault de Latour, Yvan Saeys, Gérard Socié, David Michonneau
“Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures”. Science Translational Medicine (2022) 14 (633)
DOI: 10.1126/scitranslmed.abg3083
The hematology and transplantation department of Saint Louis Hospital (APHP/University of Paris) and the INSERM U976 unit, in collaboration with the VIB (University of Gent, Belgium), deciphered the biological mechanisms associated with the immune tolerance after an allogeneic hematopoietic stem cell transplantation, in an article published on February 23, 2022 in Science Translational Medicine.
Allogeneic hematopoietic stem cell transplantation is a major curative treatment for malignant blood diseases or hematopoiesis disorders. Unfortunately, it is complicated in nearly 50% of cases by a severe immune response of donor immune cells directed against the recipient’s tissues, called graft-versus-host disease (GVHD). For reasons that are still largely misunderstood, about 1 in 4 patients develops a state of immune tolerance, allowing the permanent discontinuation of immunosuppressive drugs without the occurrence of GVHD. In a work co-directed by Dr. David Michonneau and Professor Gérard Socié (INSERM U976, Department of Hematology and transplantation, Saint Louis Hospital) and Professor Yvan Saeys (Data Mining and Modeling for Biomedicine, VIB, Gent university, Belgium), the authors studied the immune system of these so-called “tolerant” patients. The authors relied on two independent cohorts of patients from Saint Louis Hospital and the national multicentre biological collection Cryostem (https://www.cryostem.org/en/). Using blood samples from 110 transplanted patients and their healthy donors, the researchers studied all immune cell populations, gene expression profiling and the whole metabolome. They then used bioinformatics approaches to model the interaction between all these parameters. By establishing the complete mapping of the immune system of transplanted patients and its activation status, the authors highlighted the biological mechanisms that lead to the remodeling of the immune system and the emergence of immune tolerance after transplantation. By identifying new biological pathways involved in the regulation of the immune response, this work paves the way for new therapeutic approaches for the prevention or treatment of GVHD.