Given the recent role shown for IL-36 in the pathogenesis of IBD and the fact that the long standing chronic inflammation seen in IBD is known to predispose to the development of colitis associated colon cancer, we hypothesise that IL-36 may play a role in the pathogenesis of colon cancer. To determine this my sponsors’ team has generated preliminary data showing that expression of both IL-36β and IL-36γ is significantly increased in tumour tissue from colon cancer patients versus matched adjacent non-tumour tissue . This data suggests that these cytokines may play a role in colon cancer. The aim of this project therefore is to comprehensively determine the expression of all three IL-36 cytokines, the IL-36R and its antagonist in colon cancer and to identify whether expression of these alters with tumour grade and stage. To address this, I aim to complete the following objectives: 1. To characterise the expression of IL-36 cytokines α, β and γ, the IL-36R antagonist and the IL-36R in colon cancer at both the mRNA and protein level comparing expression in colon cancer specimens to adjacent normal tissue. 2. To investigate whether the expression of these change in accordance with increasing tumour stage and grade. The immune system is rapidly emerging as a key player in the development and progression of cancer. Whilst the body’s immune system is designed to detect and destroy cancer cells, cancerous tumours are known to produce molecules that suppress the immune response. A better understanding of this complex relationship between tumours and the immune system will allow for the development of better drugs and therapies to fight cancer. In this proposal we will explore the role of a family of recently identified immune molecules, the IL-36 family of cytokines, in cancer development and examine whether expression of these alters over the course of cancer progression. This will determine whether expression of these molecules can be used to predict cancer development and progression.