The origins of the serious LCH cancer disease have been identified by researchers from Karolinska Institutet in collaboration with Karolinska University Hospital. The findings presented in Sciences Immunologie may lead to new targeted treatments.
Langerhans cell histiocytosis (LCH) is a serious form of cancerous disease that mainly affects children and can be fatal in severe cases. About five to ten children contract the disease in Sweden each year, usually before the age of ten.
LCH is a disease in which the cancerous mutation occurs in immune cells, which otherwise have the task of detecting and eliminating cancerous cells.
“The origin of LCH cells has been debated for decades. Some researchers are convinced that LCH is derived from a certain type of immune cells called dendritic cells, while others think it comes from related cells called monocytes,” says Egle Kvedaraite, a physician and researcher in the Department of Biochemistry. Medicine and Biophysics of the Karolinska Institute and first author of the new study.
Researchers from the Karolinska Institutet together with scientists from the Singapore Immunology Network and the University of Newcastle have now been able to show that both theories are close to the truth. The researchers combined so-called single-cell sequencing, microscopy of samples and tracking of cells from patients recruited from, among other places, Karolinska University Hospital.
They found that the mutated LCH cells had properties similar to monocytes and dendritic cells, as well as a relatively recently discovered type of dendritic cell called dendritic cell type 3 (DC3).
“Today we know that DC3 has a distinct developmental pathway, distinct from other dendritic cells and monocytes, and knowing this was crucial in our study,” says Egle Kvedaraite.
The researchers found that the different cell types could communicate with each other to promote the development of CHL and thus create a self-reinforcing effect.
“Among the treatment options for CHL, targeted therapy can be successfully applied, but the disease recurs when targeted therapy is discontinued. This poses a serious challenge for patients, as lifelong treatment for children is not a good option given the side effects. “, says Egle Kvedaraite.
This new understanding of the origin of this type of cancer has the potential to contribute to the development of new targeted treatments.
“The results could lead to a treatment aimed at eliminating the pathological cells,” explains Egle Kvedaraite.
The research was supported by grants from the Erik and Edith Fernström Foundation for Medical Research, Swedish Childhood Cancer Foundation, Histiocytosis Association, VIVA Foundation for Children with Cancer, Wellcome Trust, CRUK Biomarker Project , Histio UK and Bright Red.
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