Deciphering the role of SOWAHC in Langerhans cell histiocytosis

This project has been approved for funding - the activation procedure is still pending

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2023

 

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasia that predominantly affects children but also strikes adults. It has variable clinical presentations ranging from single indolent lesions to fatal multi-system disease.  LCH can hit various tissues wherein abnormal innate immune system cells resembling dendritic cells (DCs) accumulate, producing granulomatous lesions. These cells invariably show increased survival and reduced motility, yet genetic alterations account for only a fraction of LCH cases. Therefore, the relationships between genetic mutations and clinical features, response to therapy, and LCH outcome cannot be predicted.

 

What mechanism drives LCH in patients whose abnormal DCs have no overt genetic alterations? Are these mechanisms operational in all patients? Can they be exploited to predict clinical presentations, risk assessment, and treatment response? 

These outstanding questions must be urgently answered for LCH patients and their families to keep hoping for effective disease management. Yet, this requires multidisciplinary studies beyond the capacity of single laboratories or institutions. 

 

We gathered a multicentre team with cutting-edge expertise in cancer-cell biology, immunology, and clinical approaches to LCH, to investigate the role of SOWAHC in LCH. This project builds on compelling preliminary data showing that SOWAHC regulates the cytoskeleton, holding promise to unearth novel LCH-relevant druggable pathways modulating DC survival and migration. Our research plan capitalizes on single-molecule and cellular studies, LCH mouse models, a large LCH biobank, and advanced imaging and genomic technologies.

 

We anticipate that this work will be a stride towards a better risk assessment and innovative treatment options for LCH patients.