Our goal is to better understand the biology of human antigen-presenting cells in health and pathology, in order to manipulate the properties of these cells for disease treatment, in particular in cancer. To achieve this, we combines studies of human cells directly isolated from tissues, in vitro models using human cells, and in vivo models in mice.

Recent contributions

In the past few years, we have focused our research on the analysis of human dendritic cell subsets. The main questions we wanted to address were:
1- what are the different DC subsets in humans ?
2- is there a functional specialization of human DC subsets ?

We found that human DC, like mouse DC, can be divided into resident DC (which remain in lymphoid organs during their entire lifespan) and migratory DC (which are present in peripheral tissues and migrate to draining lymph nodes). We showed that, while the intracellular mechanisms enabling efficient cross-presentation were conserved between mice and humans, the functional specialization for cross-presentation was different between mice and human DC subsets. Finally, we identified and characterized the human equivalent of inflammatory DC, which differentiate from monocytes during inflammation, and found that human inflammatory DC, but not inflammatory macrophages, are potent inducers of Th17 cells.

On-going projects

The aims of our current research are:

1- to characterize the functional specialization of human antigen presenting cells, in healthy conditions and in a tumoral environment.
Numerous studies in mice have shown that DC are a heterogenous population comprising several subsets that differ in their phenotype and ontogeny. Mouse DC subsets also possess distinct functions, leading to the concept of « division of labor » between DC subsets. Our knowledge of the functional specialization between human DC remains incomplete.

2- to unravel the molecular regulators that drive monocyte differentiation towards DC versus macrophage
Monocytes have long been known to be recruited to sites of inflammation and to differentiate in situ into monocyte-derived macrophages and monocyte-derived DC. What environmental cues drive monocyte fate towards macrophages versus DC, and what transcription factors orchestrate this process is to be established.

3- to manipulate monocyte differentiation in order to improve anti-cancer therapies
Despite the efficacy of immune checkpoint blockade, there is still room for improvement as a majority of patients do not respond to the therapy. Monocyte-derived macrophages are major immuno-suppressors in the tumor micro-environment. We aim to exploit our findings on monocyte differentiation to improve the efficacy of anti-cancer therapies.