Project 5 : Heterogeneity and commitment of suppressive myeloid cells

Research Topic

Juliette Ferrant (PhD student); Mathieu Lesouhaitier, MD (PhD student); Murielle Grégoire, PhD (engineer); Florence Jouan (engineer); Simon Le Gallou, PhD (engineer); Cédric Ménard, PharmD PhD (associate professor); Jean-Marc Tadié, MD PhD (professor); Mikael Roussel, MD PhD (professor)

Myeloid regulatory cells (MRCs) include myeloid derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs). These cells impair T and NK cell activities by numerous mechanisms. We previously demonstrated that the overall increase of monocytes in peripheral blood of high-grade DLBCL is related to an increase of functional myeloid MDSCs (M-MDSCs) (Azzaoui Blood 2016). Furthermore, MDSCs were also studied in sepsis patients as a non-cancer inflammatory context demonstrating the specific mechanisms of immune suppression mediated by myeloid cells in lymphomas vs septic shock (Uhel AJRCCM, 2017; Gregoire J Leukoc Biol, 2017). Finally, we demonstrated that FL TAMs contribute to tumor growth through the production of high amounts of IL-15 and the overexpression of DC-SIGN, able to crosslink specifically the oligomanosylated BCR from FL B cells (Epron Leukemia 2012; Amin Blood 2015). However, MRC heterogeneity in situ in relationship with their capacity to inhibit immune response and/or to directly activate malignant B cells has not been explored so far. We thus developed mass cytometry approaches to decipher the heterogeneous myeloid compartment in normal and lymphoma tissues (Roussel J Leukoc Biol 2017; Roussel Cancer Immunol Immunother, 2020).

Specific aims adressed in our project

Using human and xenografts samples, we perform high dimensional analysis and modeling of stromal cell/macrophages interactions in vitro to investigate:

  • the functional heterogeneity of the myeloid regulatory compartment in healthy, reactive, and lymphoma tissues
  • the crosstalk between myeloid cells and malignant B cells or cells from the tumor microenvironment