The ageing tumour microenvironment in ER+ breast cancer - identifying age-associated regulators of cytotoxic T-cell infiltration and activity
Closing date: 04/04/2025
CRUK Black Leaders in Cancer Non-Clinical PhD Scholarship: The ageing tumour microenvironment in ER+ breast cancer – identifying age-associated regulators of cytotoxic T-cell infiltration and activity
Lead Supervisors: Dr Frances Turrell
Co-Supervisors: Dr Jamie Honeychurch, Prof. Rob Clarke, Prof. Cliona Kirwan
Applications Deadline: Friday 4th April 2025
Interviews: Week commencing 28th April 2025
Non-Clinical Studentship start date: September 2025
Project Keywords: Tumour microenvironment, Immunotherapy
Research Opportunity: Non-Clinical Studentship leading to the award of PhD
Project Outline
Immunotherapy has revolutionised cancer treatment in recent years with impressive anti-tumour activity and clinical benefit observed in a range of cancers, including triple-negative breast cancer. However, oestrogen receptor-positive (ER+) breast cancers, 75-80% of all breast cancers, respond poorly to immune checkpoint blockade (ICB), in part due to low numbers of tumour-infiltrating lymphocytes (TILs). The lack of immunocompetent ER+ and, given patient demographics, age-appropriate preclinical models has severely hampered elucidation of the mechanisms of immune regulation and resistance to ICB in this disease subtype.
We have characterised syngeneic ER+ mouse mammary tumour models (Turrell et al. (2023) Nature Cancer), including ten single-cell clones which, following orthotopic injection into BALB/c mice, form ER+ or ER–/ERlow mammary tumours with divergent patterns of TILs: ER+ clones form CD8+ T-cell-excluded tumours; ER-/low clones form CD8+ T-cell-infiltrated tumours. Strikingly, for all clones, CD8+ T-cell tumour infiltration is substantially reduced in aged (15-18-month-old) mice. Using these unique models the student will profile ER+ and ER-/low tumour microenvironments in immunocompetent young and aged mice by flow cytometry, immunohistochemistry/immunofluorescence and Luminex cytokine profiling. The association of identified stromal/immune subsets or factors with CD8+ T-cell infiltration, ER-positivity and age will be determined in primary ER+HER2– breast cancer patient samples, and in vitro functional assays with age-associated subsets/factors will be performed to assess their impact on T-cell function (e.g. proliferation). Aged ER+ mammary tumour-bearing mice will be treated with agents targeting the immunosuppressive mechanism identified, before combining therapeutic strategies to increase tumour CD8+ T-cell infiltration with ICB regimes.
The characterisation of novel syngeneic models for immunotherapy studies and research into immune regulation in ER+ breast cancer will provide substantial advancement to the field, while uncovering mechanisms of T-cell exclusion and novel approaches to enhance sensitivity of ER+ breast cancers to ICB that are tailored to the older patient population.
Applications for this project are now open. Please complete your application on the Windsor Fellowship website.
About Dr Frances Turrell (project Lead Supervisor)
Dr Frances Turrell joined the University of Manchester Division of Cancer Sciences in February2024where she leads theTumour Microenvironment and Metastasis Group. Her group focusses on the role of the microenvironment in breast cancer progression, metastasis and response to therapy. Frances did her PhD at the MRC Cancer Unit, University of Cambridge withDr Carla Martins before moving to the Institute of Cancer Research in London for her postdoctoral training in Professor Clare Isacke’s group.It was there that Frances developed syngeneic mammary tumour models to study immune control of oestrogen receptor-positive breast cancer progression and metastatic relapse.
Key information
Before submitting an application, please ensure you have read the information below about the funding arrangements and eligibility for Non-Clinical Studentships.
We also encourage you to get in contact with the lead supervisor to discuss the project and any particulars.
Further information is available on the Non-Clinical PhD Studentships webpage.
Our Non-Clinical PhD Studentships are usually funded for four years, with funding covering:
- Project running costs
- University tuition fees university tuition fees (at the UK rate, with some scholarships available for high-performing EU/International candidates)
- An annual stipend of £21,000 to help with living costs
Studentships are highly competitive and so we encourage you to contact any supervisors who you are interested in working with before applying for our Non- Clinical PhD Studentships.
International Candidates
The University of Manchester aims to support the most outstanding applicants from outside the UK.
We are able to offer a limited number of bursaries to high-performing EU and international candidates, covering PhD fees only. Bursaries do not include financial support for visa/health surcharges.
We assess each EU and international candidate’s suitability for a bursary at the application and interview stages.
This programme is aimed at students from Black heritage backgrounds pursuing a PhD in cancer-related fields. This scheme is open to people who self-identify as being from a Black heritage background, including a mixed background, for example: Black African, Black Caribbean, Black Other, Mixed background (to include Black African, Black Caribbean or other Black backgrounds).
The funding for this studentship covers students with UK Home tuition fee status only. However, the CRUK Manchester Centre are able to offer a number of overseas fee scholarships to candidates deemed appointable at interview. These scholarships cover fees only and do not cover health/visa surcharge costs.
The standard CRUK Manchester Centre PhD programme and studentship academic eligibility criteria are:
- A first or upper second-class honours degree (or equivalent from a non-UK university) in a relevant subject.
- Appropriate research experience as part of, or outside of, an undergraduate or masters degree course in a relevant subject.
- Appropriate English language skills.
Applications for this programme are now open. Please follow the steps below to complete your application:
Step 1: Contact the MCRC Training team to discuss your suitability for your chosen project.
Step 2: Visit the Windsor Fellowship website for further details and to log your application with them.
Step 3: Please then submit a full application for a BLiC PhD on The University of Manchester application portal.
Key dates
- Applications open: Monday 3rd March 2025
- Application deadline: Friday 4th April 2025
- Interviews: Week commencing 28th April 2025
- Start date: September 2025
Useful Links
Submit your application
Interested in applying for this opportunity? Go to the Windsor Fellowship website to submit your application.
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