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(MCRC Non-Clinical) NK cell control of tumour growth dependent on the inflammatory environment

Project Description

Arguably, immune therapies for cancer are at a tipping point. Undoubtedly, there are many more successes to come. Understanding the mechanisms behind a strong anti-tumour immune response will surely seed new ideas for immune therapies. As well as this, identifying factors that control immune cell infiltration into tumours will lead to identifying biomarkers for patients likely to respond favourably.

Recently, we have uncovered a critical role for NK cells in anti-tumour immune responses dependent on inflammation induced in the tumour via the cyclooxygenase (COX)-2 pathway. Preliminary data has identified that a genetic signature comprising COX-2-induced tumour promoting factors and NK cell anti-tumour mediators can predict overall patient survival and response to checkpoint inhibitor therapy (specifically PD-1/PD-L1 blockade). However, much of the work has been correlative and centred on the relevant genetics; a major gap in our knowledge is in understanding precisely how this works at the level of immune cell-tumour cell interactions. Key questions include determining which types of NK cells infiltrate tumours, what recruits NK cells to tumours and whether or not tumour-infiltrating NK cells directly recruit other immune cells such as DCs and T cells. Crucially, it is vital to understand how the anti-tumour NK cell responses differ in COX-competent and COX- incompetent tumours.

Thus, this project will utilise state-of-the-art high resolution microscopy techniques (developed and used effectively in Davis’s laboratory) to evaluate immune cell, and especially NK cell, infiltration in COX-competent and COX-incompetent tumours. In parallel, a series of in vitro studies will investigate the mechanisms for NK cell migration towards tumours as well as the subsequent consequences for NK cell activation. In short, our overarching aim is to establish how inflammation impacts NK cell-mediated immune responses in different tumours, with a view to translating our findings to develop novel immune therapies and biomarkers.

Entry Requirements
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in relevant subject. A related master’s degree would be an advantage.

Funding Notes

The Studentship will cover an annual stipend (currently at £19,000 per annum), running expenses and PhD tuition fees at UK/EU rates. Where international student fees are payable, please provide evidence within your application of how the shortfall will be covered (approximately £17,000 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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