Histiocytic Diseases

A major field of research at the Fiona Elsey Cancer Research Institute (FECRI) is directed towards understanding the basic biology of histiocytic diseases. We have been studying a human form of histiocytosis called Langerhans cell histiocytosis (LCH) for many years. In this disease, cells called Langerhans cells (LCs) accumulate in various tissues to form cancer-like lesions. The causes and mechanisms controlling the development of LCH are presently unknown.

The symptoms and pathology of LCH in humans are similar to some forms of animal histiocytosis so we have recently expanded our human LCH research to include canine histiocytic diseases. All of the various forms of histiocytosis share the pathological characteristic of excessive numbers of cells called histiocytes, which include macrophages, monocytes, dendritic cells and LCs. Because of similarities in the veterinary and human pathology, we anticipate that research on lesions from animals will advance our understanding of these diseases in both humans and animals.

The most frequently occurring form of this disease in dogs is the canine histiocytoma. As with humans, these lesions are more common in young animals and often require surgical removal. With the pet owners’ informed consent, we examine a portion of the tissue that has been removed by veterinary surgeons. Our research does not involve any live animal experimentation.

The aim of our research is to evaluate the types of cells that occur within both human and canine lesions. By examining these cells, we hope to uncover the mechanisms involved in the development and progression of these disorders, and in doing so, advance our knowledge of the defective biological pathways involved. Any insights into the cause or progression of histiocytic disorders may contribute to the understanding of not only these diseases, but also to the overall understanding of other human and animal immune system diseases, including how cancers evade the normal immune system.

Many different types of inflammatory cells can be found within LCH and histiocytoma lesions but our focus is to examine LCs (CD1a+ cells) and T-cell subsets (CD3+ cells). The CD1a marker is used in the diagnosis of a number of histiocytic diseases, including LCH. Normal LCs act as antigen presenting cells, playing a central role in the initiation of an immune response by their interaction with T-cells. The figure shows the interaction of a CD3+ T-cell (red) with a CD1a+ LC (brown) in an LCH lesion. We are also examining the types and roles of the different T-cell subsets that occur in histiocytic lesions. Analysis of these cell types provides us with vital clues as to how the cellular composition in lesions differs to normal tissues. 

This project has been approved by the human research ethics committees (HREC) at Ballarat Health Services and St John of God Health Care (BHS & SJOGHC), Federation University Australia and head office of St John of God Healthcare Ethics Committee. It has also been approved by the Animal Ethics Committee (AEC) at Federation University Australia.

Our histiocytic disease research is possible due to the generosity of human patients, pets and pet owners who have kindly donated tissue following a medical procedure. We wish to thank these anonymous donors for their highly valued contributions.

Scientific Collaborations

  • Prof Jan-Inge Henter, Karolinska Institute, Stockholm, Sweden, for providing Langerhans Cell Histiocytosis (LCH) samples
  • Dr Rob Page, Eureka Veterinary Group, Ballarat, Australia, for providing caninine histiocytoma samples
  • Dr Peter Moore, Professor of Pathology, UC Davis, School of Veterinary Medicine, Pathology, Microbiology and Immunology, California, USA for providing canine reagents