Francis Crick Institute scientists have developed a mouse model that shows that cancers of dendritic cells - a type of immune cell that usually play a central role in anti-cancer immunity - are possible.
Dendritic cells are a type of cell in our immune system whose job is to bring antigens - such as foreign substances and pathogens - to the attention of our immune system.
The findings indicate that some some human disorders characterised by too many of a type of cell called histiocytes, such as Langerhans cell histiocytosis, could be caused by dendritic cells or their precursor cells becoming cancerous.
Caetano Reis e Sousa of the Crick (currrently based at Lincoln's Inn Fields) explained: "Dendritic cells have a central role in the initiation of anti-cancer immunity. As cancers of dendritic cells are very rare in humans, it has been argued that the capability of dendritic cells to initiate anti-cancer immunity might prevent dendritic cells from forming cancers themselves."
Dr Reis e Sousa's team investigated whether this was true by generating genetically engineered mice in which dendritic cells and their precursors expressed a strong cancer-promoting gene.
This resulted in the mice rapidly developing dendritic cell cancer. Even a very low number of oncogene-expressing dendritic cells was sufficient to lead to cancer development.
The researchers also carried out cell transfer experiments by transplanting dendritic cells with cancer-promoting genes into mice with normal and deficient immune systems. The mice with normal immune systems were able to reject the dentritic cells, but the mice with defective immune systems were not able to.
Jan Böttcher (in Dr Reis e Sousa's lab) said: "Our findings show that dendritic cells can, in principle, give rise to cancer in mice. This suggests that some human histiocytic disorders could be caused by dendritic cells or their precursors becoming cancerous, similar to this mouse model. However, this requires further investigation.
"This mouse model also enabled us to generate cell lines from cancerous dendritic cells - these will provide a great tool for further research into dendritic cells."
The paper, Oncogenic Transformation of Dendritic Cells and Their Precursors Leads to Rapid Cancer Development in Mice, is published inThe Journal of Immunology.
