Using tumour evolution to understand the epigenetic and transcriptional adaptations of cancer to host immunity

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PhD project strategic theme: Biosciences for an integrated understanding of healthThe immunosuppressive mechanisms operating within tumours are incompletely resolved. T cells have a powerful ability to recognise and kill cancer cells but their function is often suppressed within tumours limiting effective anti-tumour immunity and immunotherapy. According to the cancer immunoediting hypothesis, selective pressure from the adaptive immune system drives genetic changes such as antigen-loss variation to enable cancers to escape T cell immunity. We hypothesise that a broader set of epigenetic and transcriptional adaptations must occur to enable cancer cells to evade adaptive immunity. Using carcinogen-driven tumours that have developed in mice with defined defects in adaptive immunity, we will characterise the genome-wide epigenetic and transcriptional adaptations of cancer cells to host immunity and immunotherapy, testing the functional consequence of selected adaptations using genetic approaches.