Dr Jamie Honeychurch, Dr Anne Armstrong
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
About the Project
Metastatic breast cancer remains a leading cause of death in women meaning that there is a clear demand for novel, more effective treatments. An exciting new possibility is to utilise the patient’s own immune system to eradicate malignant disease. Data suggests that infiltration by immune cells, including T-lymphocytes, correlates with better response to chemotherapy, and acts as an independent prognostic indicator in breast cancer patients. Preliminary data from early phase clinical trials targeting immune checkpoints which negatively regulate anti-cancer immune responses also show great promise. Thus, there is currently considerable interest in developing strategies to enhance the generation of anti-tumour immunity.
Histone deacetylase (HDAC) inhibitors are a novel class of compounds, known to induce tumour cell death. However, recent evidence also suggests that they are able to modulate the host immune system and enhance tumour immunogenicity. Pre-clinical evidence demonstrates that combination of HDACi with immuno-regulatory antibodies can enhance therapeutic responses in solid cancers such as melanoma. HDACi are now gaining approval for use in breast cancer, although it remains poorly understood as to how HDACi may modulate immune responses in this setting.
Thus, this project aims to assess whether treatment of breast cancer cells with HDACi can induce immunogenic cell death and immuno-phenotypic changes, which result in the generation of potent tumour-specific CD8+ T-cell responses and how this may be enhanced through targeting of immune checkpoints. The project will utilise pre-clinical orthotopic breast cancer models as well as human cell lines and primary breast tumour. Immunogenic cell death and immune response will be characterised using multi-parameter flow cytometry, immunoblot analysis and a range of immuno-assays. Ultimately, the data generated in this project will be used to guide the development of effective therapeutic regimen which may be translated to clinical application.
This Clinical Research Training Fellowship will be funded by the CRUK Manchester Centre, and are usually three years in length, with the option to extend to four years under certain circumstances.
Please formally apply via the University of Manchester online system, and select PhD Cancer Sciences. Include your CV, two reference letters (or names of referees) with a covering letter (500 - 750 words max) indicating your first choice project and explaining why you want to apply. Please also comment on your suitability for the post, giving an overview of your relevant experience and training.
More information about the CRUK Manchester Centre PhD Training Scheme, including the application process, can be found on our website: http://crukcentre.manchester.ac.uk/Training/PhD-Training-Scheme.
Funding Notes
The Fellowship 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 with your application of how the shortfall will be covered (approximately £16,000 per annum).
All applicants must:
• hold a minimum upper second class (or equivalent) undergraduate degree in relevant subject
• be post-registration clinicians and ideally have a specialist training post
• have been resident and worked within the EEA (European Economic Area) for at least three years prior to application
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