Research identifies causes of disorder in kids that resembles cancer

Young children are most commonly affected with Langerhans’ Cell Histiocytosis (LCH), a lethal cancer-like illness that, in severe cases, can be fatal. Five to ten children in Sweden are affected by the sickness each year, generally before the age of 10. The causes of the severe cancer-like illness LCH have been identified by researchers from the Karolinska Institutet and the Karolinska University Hospital. The research published in Science Immunology may spur the creation of novel, specialised treatments. In the case of LCH, immune cells, which are normally tasked with identifying and destroying cancer cells, get a malignant mutation.

“The origin of the LCH cells has been discussed for decades. Some researchers are convinced that LCH is derived from a certain type of immune cell called dendritic cells, while others believe that they come from related cells called monocytes,” says Egle Kvedaraite, a doctor and researcher at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet and first author of the new study.

Scientists from Newcastle University, Singapore Immunology Network, and Karolinska Institutet have now been able to demonstrate that both ideas are almost accurate. The study’s authors used so-called single-cell sequencing with sample microscopy, cell tracking, and patient recruitment from places like Karolinska University Hospital. They found that mutant LCH cells shared characteristics with dendritic cells, monocytes, and a recently identified form of dendritic cell, known as dendritic cell type 3. (DC3).

“Today we know that DC3 has a separate pathway of development, separate from other dendritic cells and monocytes, and knowledge of this was crucial in our study,” says Egle Kvedaraite

It was found by researchers that the various cell types might interact with one another to encourage the growth of LCH and therefore produce a self-reinforcing effect.

“Among the treatment options for LCH, targeted therapy can be successfully applied, but the disease comes back when the targeted treatment is discontinued. This poses a serious challenge for patients, as a lifelong treatment for children is not a good option given the side effects,” says Egle Kvedaraite.

This new knowledge of the cause of this particular form of cancer has the potential to aid in the creation of innovative, tailored therapies. “The findings could lead to a treatment aimed at eliminating the pathological cells,” says Egle Kvedaraite.

Grants from the Histiocytosis Association, the VIVA Foundation for children with cancer, the Swedish Childhood Cancer Foundation, the Erik and Edith Fernstrom Foundation for Medical Research, the Wellcome Trust, the CRUK Biomarker Project, Histio UK, and Bright Red helped to support the study.