Using tumour evolution to understand the epigenetic and transcriptional adaptations of cancer to host immunity
Lead Research Organisation:
UNIVERSITY OF CAMBRIDGE
Department Name: Pathology
Abstract
PhD project strategic theme: Biosciences for an integrated understanding of health
The 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.
The 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.
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