UCL Cancer Institute

Dendritic cell Immunotherapy

Group Leader: Dr Clare Bennett

Understanding how DC control immunity is essential for the development of novel immuno-therapeutic strategies against leukaemias and other cancers. The skin contains multiple phenotypically and spatially distinct DC populations, in particular Langerhans cells (LC) in the epidermis and dermal DC populations in the dermis. Our group is focused on understanding the functional relevance in vivo of the presence of these distinct DC populations for the development and control of skin immune responses. To this end we have a number of models in which different skin DC can be inducibly ablated in vivo.

We work closely with Dr Ronjon Chakraverty (Transplant Immunology group) and have a PhD students on collaborative projects.

Research interests

Targeting skin DC for leukaemia immunotherapy

The high numbers of accessible DC in the skin compared to other vaccination sites has made the skin an attractive target for vaccination protocols, and cutaneous vaccination has been shown to elicit potent systemic cellular immune responses in pre-clinical immunisation models. However, it is not known which skin DC are required to prime functional protective T cells following cutaneous immunisation. One of the aims of our lab is to use cutaneous vaccination with lentiviral vectors to investigate the requirement for different DC in the generation of post-vaccination immunity. The goal of our work is to address the feasibility of targeting skin DC via cutaneous lentiviral vaccination to prime functional anti-leukaemia T cell responses in vivo. This research, with that of our collaborators, will lead to the design of superior vaccination strategies for leukaemia immunotherapy.

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Defining the role of DC in GVHD (with Dr Ronjon Chakraverty)

Donor T cells that have been infused as part of blood or bone marrow transplants become activated in response to recipient allo-antigens. This response may result in the destruction of recipient tumours (graft-versus-tumour) but can also lead to immunopathology due to the recognition of allo-antigens at sites such as the skin or the gut (graft-versus-host disease). In order to understand the mechanisms driving GVHD, and therefore to be able to separate beneficial graft-versus-tumour responses from GVHD, we have exploited our depletion models to specifically address the role of DC in GVHD. We have demonstrated that conventional recipient DC populations are required to activated donor T cells, but that LC are required to ‘license’ in-coming donor T cells to cause epithelial cell damage. Thus different DC populations interact with donor T cells at temporally and spatially distinct phases of the T cell response.



Figure 2.   Photomicrographs showing the development of immunopathology (GVHD) in inflamed LC-competent but not LC-depleted skin.

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