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Mapping the Spatial Heterogeneity and Ontogeny of Pathogenic Dendritic Cells in Langerhans Cell Histiocytosis
Principal Investigator:
Florent Ginhoux
Gustave Roussy,
Villejuif, France
Date of Award:
December 2025
Amount of Award:
50,000
This project was made possible in partnership with the Histiocytosis Association of Canada (HAC).
Layperson Summary:
This project focuses on Langerhans Cell Histiocytosis (LCH), a rare disease in which abnormal immune cells build up in tissues and cause damage. These cells are known to carry specific markers (CD1a and CD207) and often contain a mutation called BRAF V600E. However, we still don’t fully understand where these abnormal cells come from, what causes them to behave the way they do, and how they are organized within affected tissues.
Our project aims to study the exact location and types of immune cells, especially the harmful ones, inside the tissue lesions found in LCH. We are particularly interested in how these mutated cells differ in their positioning and interaction with other immune cells. Interestingly, our previous research found similar abnormal immune cells in lung tumors, suggesting there may be a shared process driving both diseases. In this study, we will compare LCH lesions to lung tumor samples to uncover common patterns.
To do this, we will use cutting-edge technology to look at gene activity, genetic mutations, and protein patterns within the tissue itself, while preserving their original location in the tissue. These tools (called Xenium, Visium HD, and MACSIMA) help us map what’s happening at a very detailed level, giving us a 3D picture of how these cells interact. This project is directly relevant to histiocytic disorders because it addresses one of the biggest unknowns in LCH: how the disease starts and spreads. By understanding the early stages and environment of LCH, we can find better ways to diagnose and treat it. Patients with LCH could benefit in several ways. Our research could lead to the discovery of new biomarkers making diagnosis easier and earlier. These biomarkers could also help doctors monitor how well treatments are working or point to new, more effective therapies. Ultimately, this work could bring real progress in the care and outcomes of people living with LCH.