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(MCRC Clinical - Leeds-Manchester) Improving the response to neoadjuvant chemotherapy in advanced colon cancer: the relationship between tumour immunology and the microbiome

Project Description

Colon cancer is a common cause of cancer-related mortality and outcomes are not improving at the same rate as for rectal cancer. High risk patients currently undergo surgery followed by adjuvant chemotherapy. Neoadjuvant chemotherapy has recently been shown in the international CRUK-funded FOxTROT trial to improve two year relapse-free survival in patients with advanced colon cancer. However, there are currently no validated biomarkers for predicting tumour response and the mechanisms of regression and non-response are unknown. Tumour-associated immune cells are well recognised to influence outcomes, however, their effect on the response to neoadjuvant treatment is relatively unknown. In addition, the microbiome is increasingly being recognised to play a role in cancer development and behaviour. This project will assess the role tumour-associated immune cells and the microbiome play in the response to neoadjuvant chemotherapy in advanced colon cancer.

Pre and post chemotherapy samples have already been collected from the FOxTROT trial and will undergo analysis for the numbers and location of immune cells using established methodology. In depth analysis of key immune cell subsets and immunotherapy targets will be determined using immunohistochemistry and immunofluorescence. The microbiome will be analysed through low coverage whole genome sequencing. Response will be determined using tumour regression grading and a novel tumour cell density (TCD) technique.

The project will define the effect of chemotherapy on tumour-associated immune cell populations and the microbiome in advanced colon cancer by comparing the pre-and post-treatment samples and identifying how this differs in responders and non- responders. Novel predictive signatures will be explored along with the possible mechanisms of tumour cell regression and non-regression. The use of artificial intelligence to identify immune cell populations will be investigated and TCD will be optimised as a short term pathological endpoint. The association with long term outcomes will be explored as these become available.

Entry Requirements:
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage. All applicants should be post-registration clinicians and ideally have a specialist training post. Candidates of any nationality may apply but must have been resident and working in the EEA (European Economic Area) for three years immediately before application and intend to pursue a medical career in the UK.

To submit a formal application for this studentship please make direct contact with Jo Bentley, Clinical Academic Training Programme Manager

Funding Notes

The clinical fellowships are tenable for three years. We will provide running expenses, an appropriate salary in line with the applicant’s current salary and grade, and full coverage of University PhD fees. Where international student fees are payable, please provide evidence with your application of how the shortfall will be covered (approximately £19,000 per annum).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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