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

Studentship strategic priority area:Basic and Clinical Research
Keywords: Gamma, delta, colorectal, prognostic, cancer

The Project
The 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 Opportunities
The 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 Strategy
The 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.