Team MICHONNEAU

Translational Immunology in Immunotherapy and Hematology (TIGITH)

Allogeneic hematopoietic stem cell transplantation is a curative treatment for malignant and non-malignant hematological diseases, whose efficacy relies on the allogeneic immune response directed against tumor cells, known as the graft-versus-tumor (GvT) effect or graft-versus-leukemia (GvL) effect. The main complications are graft-versus-host disease (GVHD) and relapse of the underlying hematological malignancy (leukemias, lymphomas, myelodysplastic and myeloproliferative syndromes). Our research projects aim to understand the mechanisms of the alloimmune response during GVHD or the antitumor response through multi-omic analysis of human samples from multicenter cohorts and murine models.

The PORTRAIT project (Prediction of Relapse Through Artificial Intelligence and multiomics after allogeneic HSCT) combines the use of machine learning models with clinical and multi-omic data (mass cytometry, metabolomics) to develop predictive tools for relapse after allogeneic HSC transplantation.

The alloPHAGE project (Unravelling the interplay between intestinal Bacteroides genus and antitumor immune response following allogeneic HSCT: toward phage therapy-targeted modulation of gut microbiota to prevent relapse) aims to develop murine models of allogeneic HSCT transplantation and antitumor response, and to study the impact of the gut microbiota on the regulation of the immune response against cancer cells, as well as the modulation of the fine composition of the microbiota through the use of bacteriophages, in order to improve the efficacy of this response.
Funding: ANR PRCE, INCA PLBIO, FONDATION ARC SIGNIT

Acquired aplastic anemia (AA) is a rare hematological disease characterized by immune-mediated destruction of hematopoietic progenitors, which may progress in 15 to 20% of cases toward a myeloid hematological malignancy. The HEALIA project (Hematopoiesis and Immunopathology of Acquired Aplastic Anemia) aims to characterize the immune response and hematopoiesis abnormalities underlying AA in patient bone marrow, and to determine the molecular mechanisms driving their clonal evolution. This axis relies on a multicenter cohort of bone marrow samples from the RIME biological collection of the National Reference Center for Aplastic Anemia (https://aplasiemedullaire.com/), and on the use of single-cell transcriptomic and genomic approaches.
Funding: DIM ITAC, Association Laurette Fugain, Fondation Maladie Rare, Association AA-HPN France

1 – Ambivalent functions of MAIT cells in the graft-versus-leukemia effect
While the role of conventional T lymphocytes in the GVL effect is well established, that of other immune populations remains poorly understood. Mucosal-associated invariant T (MAIT) cells, a population of so-called “innate” T lymphocytes, may play an ambivalent role in this context, acting as both effectors and regulators. Our project aims to study the crosstalk between MAIT cells and the cellular actors of this allogeneic context in order to better understand their involvement in the GVL/GVH balance, through both a fundamental and translational approach.
2 – Role of myeloid-derived suppressor cells (MDSCs) in pediatric leukemias
MDSCs are regulatory cells capable of suppressing the antitumor immune response. In adults, their presence at high levels is associated with poor prognosis in several cancers. However, they remain understudied in children, and their role in pediatric AML — a rare but aggressive blood cancer — is unknown. We have observed that MDSCs are increased after allogeneic transplantation in adults and are negatively correlated with T lymphocyte levels. This project therefore aims to characterize these cells in children with AML, analyzing their evolution during treatment, their immunoregulatory functions, and their potential impact on relapse.
Funding: Emergence UPC, Paris Kids Cancer