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

博士项目战略主题：生物科学对健康的综合理解肿瘤内的免疫抑制机制尚未完全解决。T细胞具有强大的识别和杀死癌细胞的能力，但它们的功能在肿瘤内往往受到抑制，限制了有效的抗肿瘤免疫和免疫治疗。根据癌症免疫编辑假说，来自适应性免疫系统的选择性压力会驱动基因变化，如抗原丢失变异，使癌症能够逃避T细胞免疫。我们假设，必须发生更广泛的表观遗传和转录适应，才能使癌细胞逃避获得性免疫。利用在适应性免疫存在明确缺陷的小鼠身上发展起来的致癌物驱动的肿瘤，我们将表征癌细胞对宿主免疫和免疫治疗的全基因组表观遗传和转录适应，使用遗传方法测试选定适应的功能后果。

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.