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

最近的证据表明，胰岛素信号传导对活化的T细胞的重要性，支持代谢重编程和增强病毒感染和自身免疫模型中的效应器功能。我们的研究小组已经确定，从肿瘤中提取的间质液中胰岛素水平显著降低，这表明废除的胰岛素信号传导可以部分解释肿瘤内效应T细胞的代谢抑制。我的项目将测试肿瘤微环境中的胰岛素可用性有限的假设，限制葡萄糖摄取，T细胞活化并最终阻碍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介导的敲除系统、体外功能测定、表观基因组学和转录组学技术来检验这一假设

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