Dr Jamie Honeychurch, Prof J O'Connor, Prof Kaye Williams
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
The importance of T-cell immunity to cancer outcome is increasingly recognised. Infiltration of tumours by T-cells correlates with patient survival, and immunotherapies designed to enhance T cell function, such as checkpoint blockade, have revolutionised the way in which many solid malignancies are treated. Combination with standard-of-care treatments including radiotherapy can further enhance outcome. However, tumours frequently remain unresponsive or are devoid of T-cells. Thus, understanding barriers to T cell infiltration and mechanisms of resistance to T cell killing are critical for the future development of successful anti-cancer therapies.
The tumour microenvironment (TME) displays many characteristics generally considered to be hostile to T-cells including low oxygen tension (hypoxia) and this contributes to T-cell dysfunction via several mechanisms including the recruitment of immune suppressive populations such as tumour-associated macrophages. Paradoxically, other recent evidence indicates that low oxygen tension may enhance T-cell effector function, cytotoxic potential, IFN production and formation of memory populations. Thus the exact contribution of intratumoral oxygen levels to the generation of anti-cancer immunity is unclear, particularly in response to therapy.
This project will evaluate how dynamic changes in oxygen levels during radiotherapy and immunotherapy combinations influence the generation of protective T-cell immune responses. The project will utilise pre-clinical cancer models with defined immune contexture to conduct longitudinal studies on in vivo oxygen levels using MR imaging. Oxygen dynamics will be correlated with T-cell infiltration, functional activation status and overall outcome. The impact of oxygen tension on the interaction of tumour antigen-specific T-cells with cancer targets, immune synapse formation and granule deposition will be explored ex vivo using advanced imaging techniques. Data from these studies will increase understanding of tumour immuno-biology and potentially inform clinical trial design and assess value of imaging oxygen tension as a biomarker to predict response to combination therapies.
Entry Requirement
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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