Translational Immunology in Immunotherapy and Hematology (TIGITH)

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David Michonneau

Team leader

orcid 0000-0003-4553-3065,

X : @MichonneauDavid,

BlueSky : @dmichonneau.bsky.social,

Linkedin : https://fr.linkedin.com/in/david-michonneau-94b38473

Stéphanie CHAMBAUD

Research themes

Research themes

Our research team is engaged in fundamental and translational projects aimed at unraveling the biological mechanisms underlying complications that arise after allogeneic hematopoietic stem cell transplantation. Additionally, our focus is on the immunological mechanisms underlying acquired aplastic anemia and its progression towards hematologic malignancies.

Studied Pathologies

Allogeneic hematopoietic stem cell transplantation

Graft-versus-host disease (GVHD)

Relapse

Anti-tumor immunity

Gut microbiota

Acquired aplastic anemia

Myeloid malignancies

Allogeneic hematopoietic stem cell transplantation

Graft-versus-host disease (GVHD)

Relapse

Anti-tumor immunity

Gut microbiota

Acquired aplastic anemia

Myeloid malignancies

Research areas

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for both malignant and non-malignant hematologic disorders. Its main complications are graft-versus-host disease (GVHD) and relapse of the underlying hematologic malignancy. Our research projects aim to understand the mechanisms of the alloimmune response during GVHD or antitumor response through multi-omics analysis of human samples from multicenter cohorts (mass cytometry, metabolomics, single-cell transcriptomics, gut microbiota analysis using 16S PCR or metagenomics). Our team also develops murine models of allogeneic transplantation and antitumor immune responses to design new preventive or curative therapeutic approaches for these complications.

Acquired aplastic anemia (AAA) is a rare hematologic disorder characterized by immune-mediated destruction of hematopoietic progenitors, which can evolve into a myeloid malignancy in 15 to 20% of cases. Our projects aim to characterize the immune response underlying AAA in the bone marrow of patients and to identify the molecular mechanisms driving clonal evolution in AAA. This research is based on a multicenter cohort of bone marrow samples from the RIME biocollection of the French National Reference Center (https://aplasiemedullaire.com/) and leverages single-cell transcriptomic and genomic approaches.

MAIT cells (Mucosal-Associated Invariant T cells) are lymphocytes associated with mucosal tissues and characterized by the expression of an invariant TCR α-chain, Vα7.2. Their regulatory role in the immune response remains poorly understood. The team aims to characterize the interactions between MAIT cells and other immune cell populations, particularly in the context of the alloimmune response, and to develop innovative therapies based on the generation of CAR MAIT cells to target tumor pathologies, using in vitro approaches and murine models of solid cancers.

Team members

David Michonneau
Professor, team leader
Régis Peffault de Latour
Professor
Jean-Hugues Dalles
Professor
Gérard Socié
Professor
Thierry Leblanc
Associate professor
Sophie Le Grand
PhD student
Gwendolyn Marguerit
Bioinformatic engineer
Margo Fernandez
Research engineer
Mathieu Chevalier
CRCN
Marion Lambert
Research engineer
Sophie Caillat-Zucman
Professor
Elise Diaz
Research engineer
Vivien Peux
Research engineer
Nobert Minet
Postdoc
Jennifer Bordenave
Postdoc
Liana Ghazarian
Postdoc
Charlotte Calvo
PhD student

Scientific publications

Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses

Circulating T cell profiles associate with enterotype signatures underlying hematological malignancy relapses

Nicolas Vallet  & al, Cell Host Microbe, 2023
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Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation

Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation

Nicolas Vallet & al, Blood, 2022
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Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures

Operational tolerance after hematopoietic stem cell transplantation is characterized by distinct transcriptional, phenotypic, and metabolic signatures

Laetitia Dubouchet & al, Sci Transl Med, 2022
Lire la publication
Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites

Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites

David Michonneau & al, Nat Commun., 2019
Lire la publication

Industrial partners

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Funding

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