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Dendritic Cell Immunotherapy
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.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. A challenge of cancer immunotherapy is to break the immunological tolerance that is associated with tumour development, in order to generate anti-tumour immune responses by activated T cells. LC are highly immunogenic, and activation of LC may be sufficient to break anti-tumour tolerance, and to generate a protective immune response to cutaneous cancers. In addition, LC have been shown to imprint a skin-homing phenotype on T cells primed in skin-draining LN, such that effector T cells efficiently recirculate back to the site of LC activation. We are interested in understanding the role of skin DC at different stages of a cutaneous immune response, with a view to developing improved skin-targeted strategies for cancer immunotherapy.
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