Investigation into novel immunotherapeutics which target the development of tumour associated macrophages in cancer

拟议的项目将利用自发的乳腺癌体内模型和实验室最近开发的一种新型转基因模型。这些模型将与转录组学分析、基因敲低研究和已知药物筛选一起使用，以获得对指导肿瘤相关巨噬细胞（TAM）的促肿瘤表型的关键信号的生物学洞察。一旦确定了感兴趣的靶标，将详细研究它们在巨噬细胞分化和功能中的作用。使用我们的体内模型，我们将使用活体显微镜实时跟踪TAM的募集和分化。这些发现将在人类乳腺癌以及其他肿瘤中进行临床前验证，使用体外巨噬细胞培养，肿瘤切片和在线患者生存和表达数据库。

The proposed project will utilise spontaneous in vivo models of breast cancer and a novel transgenic model that has recently been developed by the laboratory. These models will be used alongside transcriptomic analyses, gene knockdown studies, and known drug screens, to gain biological insight into the key signals which direct the pro-tumoural phenotype of tumour associated macrophages (TAMs). Once the targets of interest have been identified they will be investigated in detail for their role in macrophage differentiation and function. Using our in vivo models, we will use intravital microscopy to track the TAMs recruitment and differentiation in real-time. The findings will be preclinically validated in human breast cancer, as well as other tumours, using in vitro macrophage culture, tumour sections and online patient survival and expression databases.