Are gamma delta T cells associated with prognosis in colorectal cancer?

关键字：Gamma， delta，结直肠癌，预后，癌症项目项目将研究Gamma delta T细胞在人类结直肠癌中的预后作用。该计划将利用三组结直肠癌患者；一个筛查队列，一个ii/iii期（和一些i/iv期）队列和一个同步队列，分别作为早期、中期和晚期队列。利用免疫组化技术，除了确定γ δ T细胞在原发性肿瘤或转移性肿瘤中的特异性外，还可以确定CRC中γ δ T细胞的存在（在疾病进展的哪个阶段？）和位置（肿瘤内，基质？）。这将使我们能够了解伽马δ T细胞参与肿瘤进展过程的哪一点以及它们在哪里起作用。在确定γ δ T细胞是否确实与肿瘤相互作用后，我们将试图了解γ δ T细胞如何与其他因素相关，例如；患者的炎症状态、额外的免疫浸润（中性粒细胞等）、CRC亚型、细胞因子表达、γ δ T细胞亚群和基因组差异。这将概述伽马δ T细胞何时、何地以及如何对肿瘤进展过程施加影响，以及这些信息是否可以将伽马δ T细胞转化为预后标志物。将这些发现与同事进行的动物实验相结合，我们就可以确定如何从这一点开始推进项目。学习机会该项目将允许在IHC专业实验室的指导下发展IHC等实验室技能。除了各自实验室对结直肠癌和γ δ T细胞的深入了解外，这将为指导该项目提供所需的环境和专业知识。也有可能学习其他实验室技能，如流式细胞术和基于细胞的测定。由于大量的数据正在收集和已经收集，如基因组学，该项目将需要大量的统计分析和数据解释。通过参加讲座和可能的外部课程，将获得管理和解释数据所需的技能和经验。MRC DTP策略该项目将支持伽马δ T细胞在CRC中的作用的基础研究。这将通过进一步了解γ δ T细胞如何与CRC相互作用来实现；它们是否有效地靶向结直肠癌，是直接的还是间接的，它们在什么阶段靶向结直肠癌，最终，它们的活性是否是结直肠癌患者的预后标志物。在这个过程中，我们很可能会对γ δ T细胞生物学的基本理解做出贡献。在个性化医疗的时代，以γ δ T细胞为形式的预后标记物的发展将使我们能够根据护理和治疗的类型对患者进行分层，为他们的癌症提供最佳选择。

Studentship strategic priority area:Basic and Clinical ResearchKeywords: Gamma, delta, colorectal, prognostic, cancerThe ProjectThe project will investigate the prognostic role of gamma delta T cells in human CRC. The project will utilise three cohorts of CRC patients; a screening cohort, a stage ii/iii (and some stage i/iv) cohort and a synchronous cohort, acting as early, mid and late stage cohorts respectively. Using IHC, the presence (at which stage of disease progression?) and location (intra-tumoural, stroma?) of gamma delta T cells in CRC will be determined, in addition to whether they are specific to primary tumours or metastases. This will allow us to appreciate at which point gamma delta T cells engage in the process of tumour progression and where they act. Upon establishing whether gamma delta T cells do in fact interact with the tumour, we will seek to understand how gamma delta T cells correlate with other factors, such as; inflammatory status of the patient, additional immune infiltrates (neutrophils etc), CRC subtype, cytokine expression, gamma delta T cell subset and genomic differences. This will provide an overview of when, where and how gamma delta T cells might be exerting an influence on the process of tumour progression and whether this information can translate gamma delta T cells into a prognostic marker. Combining these findings with animal work conducted by a colleague, we can then determine how to take the project forward from that point. Learning OpportunitiesThe project will allow the development of lab skills such as IHC, under the tutelage of a specialist IHC laboratory. In addition to the in-depth knowledge of colorectal cancer and gamma delta T cells in the respective labs, this will provide the environment and expertise required to guide the project. There is also the potential to learn other laboratory skills such as flow cytometry and cell-based assays. Due to the vast amount of data being collected and already collected, such as genomics, the project will require a great deal of statistical analysis and data interpretation. Through attendance at lectures and possibly external courses, the skills and experience required to manage and interpret the data will be obtained. MRC DTP StrategyThe project will bolster the basic research into the role of gamma delta T cells in CRC. This will be achieved by furthering our understanding of how gamma delta T cells interact with CRC; whether they efficiently target CRC and if this is direct or indirect, at what stage they target CRC and ultimately, whether their activity is a prognostic marker for CRC patients. In the process, it is likely that we will contribute to the basic understanding of gamma delta T cell biology. In an era of personalised medicine, the development of a prognostic marker in the form of gamma delta T cells will allow us to stratify patients for type of care and treatment, providing them with the best options for their cancer.