Science Immunology identifies the origins of serious illness in children

Researchers from Karolinska Institute and Karolinska University Hospital have identified the origin
of LCH, a serious cancer-like disease.
The findings, published in Scientific Immunology, could lead to new, targeted treatments
.

Langerhans cell histiocytosis (LCH) is a serious, cancer-like disease that mainly affects children and can be fatal
in severe cases.
In Sweden, about 5 to 10 children develop the disease each year, usually before
the age of 10.

LCH is a disease in which cancer mutations occur in immune cells that would otherwise have the task
of detecting and removing cancer cells.

"The origin of LCH cells has been discussed for decades
.
Egle Kvedaraite, a doctor and researcher in the Department of Medical Biochemistry and Biophysics at Karolinska Institutet and first author of the new study, said: "Some researchers believe LCH comes from a specific type of immune cell called dendritic cells, while others believe they come from a related type of cell
called monocytes.
"

Researchers from the Karolinska Institute, as well as scientists from the Singapore Immune Network and Newcastle University, have now been able to show that both theories are close to fact
.
The researchers combined so-called single-cell sequencing, microscopic observation of the samples and cell tracking
of patients recruited from Karolinska University Hospital.

They found that the mutated LCH cells had similar properties to monocytes and dendritic cells, as well as a relatively new dendritic cell type, the so-called dendritic cell type 3 (DC3).

Egle Kvedaraite said: "Today we know that DC3 has an independent developmental pathway, independent of other dendritic cells and monocytes, and this understanding is crucial
in our study.
"

The researchers found that different types of cells can communicate with each other, promoting the development of LCH, which produces a self-reinforcing effect
.

"In LCH treatment regimens, targeted therapy can be used successfully, but when targeted therapy is stopped, the disease recurs
.
This presents a serious challenge for patients, as lifelong treatment of children is not a good option considering the side effects," says
Egle Kvedaraite.

This new understanding of the origins of this type of cancer has the potential to help develop new targeted therapies
.

Egle Kvedaraite said: "These findings could lead to a treatment
aimed at eliminating pathological cells.
"