Epigenetic mapping of immune cells in colorectal cancer (360G-Wellcome-209186_Z_17_Z)

A recent large-scale study of 39 different types of cancers has shown that the expression of the gene KLRB1, encoding the protein CD161, was the top predictor of favourable prognosis and overall survival. CD161 is expressed on various immune cells, including newly discovered populations such as MAIT cells and innate lymphoid cells. To identify the intratumoural cells contributing to improved prognosis, I will develop a tool for the bioinformatic enumeration of pure cell types from complex populations. As chromatin accessibility and enhancer landscape reflects cell identify better than mRNA levels, differentially accessible loci will be a unique signature for each cell type. Using state-of-the-art technologies, my key goals are to: Generate a comprehensive epigenetic signature matrix encompassing novel immune cell types Use this to deconvolute the epigenome of colorectal carcinoma tumours Directly identify the infiltrating CD161-expressing population correlated with improved survival in colorectal cancer By improving our understanding of how multiple immune populations collectively infiltrate tumours, including novel CD161-expressing cells, this work will enable future cancer immunotherapies to target protective immune subsets. Furthermore, the proposed work will provide a resource that can be easily applied to epigenetic data from other malignancies.