Whilst the Interleukin 36 (IL-36) family of cytokines have been shown to play key roles in immunity and inflammation, their role in in tumorigenesis is poorly studied and understood. Our preliminary investigations have determined that IL-36 cytokines have distinct pro-tumorigenic functions in colon cancer (CRC), and that administration of the IL-36 receptor antagonist (IL-36RA) suppresses tumour growth using a subcutaneous tumour model. The aim of this proposal is to progress these studies using both human CRC patient samples and a relevant pre-clinical CRC model in order to identify the translational potential of the IL-36R as a target for therapy. Research undertaken in this proposal will investigate: (1) the cellular and spatial expression of IL-36 receptor and the IL-36R antagonist in the tumour microenvironment; (2) the therapeutic and translational potential of targeting the IL-36R in CRC, alone and in combination with anti-cancer therapies. These studies are essential to exploit the therapeutic potential of IL-36 in malignant disease.
