Discovering the origins of the dangerous cancerous disease LCH

The origins of the dangerous disease LCH have been identified by researchers from Karolinska Institutet in collaboration with Karolinska University Hospital. Results presented in Immunology It may lead to new targeted therapies.

Langerhans cell histiocytosis (LCH) is a serious form of cancer that mainly affects children and can be fatal in severe cases. About five to ten children fall ill in Sweden each year, usually before the age of ten.

LCH is a disease in which the cancerous mutation occurs in immune cells, which would otherwise have the task of detecting and eliminating cancerous cells.

The origin of LCH cells has been debated for decades. Some researchers believe that CHL is derived from a specific type of immune cell called dendritic cells, while others believe that it comes from related cells called monocytes. »

Egle Kvedaraite, MD and researcher in the Department of Medical Biochemistry and Biophysics at Karolinska Institutet and first author of the new study

Now researchers from the Karolinska Institutet and scientists from the Immunology Network in Singapore and Newcastle University have been able to show that both theories are close to the truth. The researchers combined so-called single-cell sequencing and microscopy of samples and cell tracing from patients recruited from, among other places, the Karolinska University Hospital.

They found that the transformed LCH cells had similar characteristics to monocytes and dendritic cells, as well as to a relatively recently discovered type of dendritic cell called dendritic cell type 3 (DC3).

“We know today that DC3 has a distinct developmental trajectory, different from other dendritic cells and monocytes, and knowing this was crucial to our study,” says Eigel Kvidarait.

Researchers have found that different cell types can communicate with each other to promote the progression of CHL and thus create a self-reinforcing effect.

“Among the treatment options for CHL, targeted therapy can be applied successfully, but the disease recurs when targeted therapy is discontinued. This poses a serious challenge for patients, because lifelong treatment for children is not a good option due to side effects,” says Eigel Kvdaret.

This new understanding of the origin of this type of cancer has the potential to contribute to the development of new targeted therapies.

“The results could lead to a treatment aimed at eliminating disease cells,” explains Eagle Kvidarait.

The research was supported by grants from the Eric and Edith Fernström Foundation for Medical Research, the Swedish Childhood Cancer Foundation, the Histiocytosis Society, VIVA Children with Cancer, the Wellcome Trust, the CRUK Biomarker Project, Histio UK and Bright Red.