Investigating the role of the IGF-1 axis on the anti-cancer immune response

研究 IGF-1 轴在抗癌免疫反应中的作用

• 批准号: 2434796
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2434796
• 关键词: Investigating; role; IGF; axis; anti

The focus of this research project is the investigation of insulin-like growth factors (IGFs) as risk factors for development of cancer. In current work we are studying effects of varying IGF supply on benign and malignant prostate epithelial cells, and have made two observations that could be relevant to pro-tumorigenic effects of IGF-1. Firstly, we find that serum IGF-1 associates with altered expression of the IGF receptor (IGF-1R) in malignant prostatic epithelium. Secondly, we recently identified changes in expression of immune molecules by prostate cancer cells, which could potentially affect T cell recognition. Therefore, this project will investigate the hypothesis that a high IGF environment drives pro-tumorigenic changes in tumour epithelium, while suppressing the ability to mount an anti-tumour immune response. The student will use in vitro and in vivo models and clinical data to investigate the relationship between IGF supply and immune cell function in prostate cancer. There will also be the opportunity to analyse tissues obtained from patients recruited to an academic-led windows trial in men with early prostate cancer prior to radical prostatectomy, using multiplexed tissue markers to assess effects of IGF blockade. The student will be supervised by Dr Macaulay and her group, with co-supervision from Professor Clare Verrill to provide expertise in tissue analysis and digital pathology. Thus, this project will be a collaboration between the Department of Oncology and the Nuffield Department of Surgical Sciences. This is an exciting opportunity for training in basic and translational research to understand how effects on the tumour microenvironment contribute to the association of IGF-1 with cancer risk and progression. The long-term aims of this research are to identify mediators of high IGF-1, in order to develop novel approaches to cancer risk reduction.

该研究项目的重点是调查胰岛素样生长因子（IGFs）作为癌症发展的危险因素。在目前的工作中，我们正在研究不同的IGF供应对良性和恶性前列腺上皮细胞的影响，并提出了两个意见，可能是有关促肿瘤的IGF-1的影响。首先，我们发现血清IGF-1与恶性前列腺上皮中IGF-1 R的表达改变有关。其次，我们最近发现了前列腺癌细胞免疫分子表达的变化，这可能会影响T细胞识别。因此，该项目将研究高IGF环境驱动肿瘤上皮细胞促肿瘤发生变化的假设，同时抑制抗肿瘤免疫反应的能力。学生将使用体外和体内模型和临床数据来研究前列腺癌中IGF供应和免疫细胞功能之间的关系。也将有机会分析从招募到一个学术主导的窗口试验中的早期前列腺癌男性根治性前列腺切除术前的患者获得的组织，使用多重组织标志物来评估IGF阻断的效果。该学生将由麦考利博士和她的小组监督，由克莱尔Verrill教授共同监督，提供组织分析和数字病理学方面的专业知识。因此，该项目将是肿瘤学系和外科科学纳菲尔德系之间的合作。这是一个令人兴奋的基础和转化研究培训机会，以了解对肿瘤微环境的影响如何有助于IGF-1与癌症风险和进展的关联。这项研究的长期目标是确定高IGF-1的介质，以开发降低癌症风险的新方法。