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Find out more about Dr Clare Bennett's research on dendritic cells and cancer immunotherapy.
Dendtritic cells are essential for activating and controlling T cell immunity. In the lab we aim to exploit DC function in order to promote anti-tumour responses by T cells.
Dendritic cells (DC) are antigen-presenting cells that develop from cells in the bone marrow and sit at sites in the body which are exposed to infection, like the skin, lungs and intestine.
DC possess a unique combination of features that allow them to efficiently activate T cells in the presence of infection. Our aim is to exploit these features to activate T cells.
W e are particularly interested in the DC in the skin. In the epidermis, Langerhans cells (LC) form a network that covers the surface of the skin. In the dermis there are at least 2 types of DC, each with specific roles in skin immunity. The high density of different types of DC and the accessibility of the skin make it and attractive site to target DC for immunotherapy. However, DC do not always activate beneficial T cell responses, and they may also cause immunopathology in the skin.
Allogeneic haematopoietic stem cell transplantatoin is a proven immunotherapy for patients with some blood cancers. However, its success is limited by the recruitment of donor T cells in inflamed tissues such as skin and gut, where they attack healthy cells (GVHD). With Ronjon Chakraverty, we have a programme of work that waims to identify critical checkpoints which may control activation of donor T cells in the tissues, with the aim of uncoupling the anti-tumour response from GVHD.
W e have shown that LC are required to activated pathogenic T cells in the skin. Ongoing work in the lab now aims to address the following questions: How do interactions between donor T cells and LC, or other skin immune cells control skin pathology? Do DC control pathology in other GVHD target organs? How do changes in LC and DC populations after GVHD shape skin immune homeostasis?
W e are also interested in exploring how we can exploit DC function to generate immune responses against tumours.
We have shown that DC efficiently present antigen derived from lentiviral vectors, and activate potent effector and memory T cells responses against tumours. Our work is focused on: Understanding the interaction between DC and lentiviral vectors in more detail. Exploiting the efficiency with which DC present lentiviral antigens to T cells in order to develop new immunotherapy strategies, e.g. by manipulating DC activation.