Dendritic cells (DC) are specialised immune cells that link innate and adaptive immunity.  In the skin they function in co-operation with other immune cells, including Langerhans cells (LC), the unique macrophage population of the epidermis, and other myeloid and lymphoid populations in the dermis.  Together these cells work together to maintain skin immune homeostasis.

Our key research goals are to gain a greater understanding of LC and DC development and function within the skin, and how these processes become dysregulated in cancer and as a result of immune pathology.  We use this knowledge to develop new ways of harnessing DC for immunotherapy.

Projects in the lab are focused on:

1. Defining the plasticity and function of skin myeloid cells in GVHD.

DC have the potential to activate immune responses against tumours.  However, in other settings DC may also drive unwanted immune responses, resulting in immunopathology and tissue damage. This dichotomy is particularly relevant after bone marrow transplant when DC likely drive the anti-tumour response, but also activate donor T cells to destroy tissues such as the skin and intestine (graft-versus-host disease, GVHD).  We are interested in understanding how skin DC drive cutaneous immunopathology, and in turn, how damage to the skin alters the resident DC and LC populations.

We have shown that immune injury leads to replacement of the resident LC network by monocyte-derived cells that became functionally and transcriptionally indistinguishable from the cells they replace.  On-going work aims to address fundamental questions about the intrinsic and extrinsic signals that control monocyte differentiation in the epidermis, and what the consequence of LC replacement is for cutaneous immunity. 

2. Harnessing DC for cancer immunotherapy

The development of T cell immunotherapies has revolutionised our approach to treating cancer.  However, despite this many patients and cancers do not respond, and there is a need to build on this success to improved treatment outcomes.  DC are essential for T cell-mediated rejection of tumours, but we still know little about how DC may work with T cells to promote tumour destruction after immunotherapy.  We have a number of projects in the lab that are seeking to apply our understanding of DC biology to improving immunotherapeutic treatments of across cancers.