Elucidating the effects of insulin signalling on T cell metabolism and effector function within the tumour microenvironment

最近的证据表明，在病毒感染和自身免疫模型中，胰岛素信号对激活的T细胞、支持新陈代谢重新编程和增强效应器功能的重要性。我们的团队已经发现，从肿瘤中提取的间质液体中的胰岛素水平显著降低，这表明被取消的胰岛素信号可以部分解释肿瘤内效应T细胞的代谢不足。我的项目将检验这样一个假设，即胰岛素在肿瘤微环境中的可获得性是有限的，限制了葡萄糖的摄取，限制了T细胞的激活，最终阻碍了有效的抗肿瘤免疫和免疫治疗。我们将使用小鼠肿瘤模型、CRISPR介导的基因敲除系统、体外功能分析、表观基因组学和转录切割技术来验证这一假设

Recent evidence has shown the importance of insulin signalling for activated T cells, supporting metabolic reprogramming and enhancing effector function in viral infection and autoimmunity models. Our group has identified that insulin levels are profoundly diminished within interstitial fluid extracted from tumours, suggesting that abrogated insulin signalling could partially explain metabolic insufficiencies of effector T cells within tumours. My project will test the hypothesis that insulin availability in the tumour microenvironment is limited, restricting glucose uptake, T cell activation and ultimately hampering effective anti-tumour immunity and immunotherapy. We will test the hypothesis using murine tumour models, CRISPR-mediated knockout systems, in vitro functional assays, epigenomic and transcriptomic techniques