(MCRC Clinical) Sustaining adoptive T cell immunity: defining the role of activated dendritic cells in solid tumours

About the project

About the Project Adoptive cellular therapies, in which tumour-reactive T cells are expanded or engineered before being transferred into patients, have transformed the treatment of some blood cancers and are showing increasing promise in solid tumours. However, responses in solid cancers are often short-lived because transferred T cells fail to persist and progressively lose their ability to attack cancer cells within the tumour. Understanding what sustains these cells after they enter tumours is therefore a major challenge for improving cellular immunotherapy. Dendritic cells (DCs) are best known for initiating immune responses by activating naïve T cells. Our recent work identified a distinct population of CCR7-expressing activated dendritic cells (actDCs) that is essential for effective anti-tumour immunity. Notably, we found that actDCs are also required for successful adoptive T cell therapy, even when fully activated tumour-specific T cells are transferred. Without actDCs, transferred T cells rapidly become dysfunctional, revealing an unexpected role for dendritic cells in maintaining ongoing anti-tumour responses. This project will determine how actDCs sustain transferred T cells within solid tumours. Using unique genetically engineered mouse models developed in our laboratory, we will establish which dendritic cell populations are required, whether continued recognition of tumour antigens is necessary, and which signals provided by actDCs maintain T cell expansion, survival, localisation and function. Reporter models will allow us to visualise how actDCs and transferred T cells interact within tumours and how these interactions change during therapy. Crucially, mechanistic discoveries will be connected directly to clinical cellular immunotherapy through analysis of longitudinal tumour and blood samples from patients receiving immunotherapies, including adoptive cellular therapies. By defining how the tumour immune environment supports or undermines transferred T cells, this project aims to identify new strategies to improve the persistence and effectiveness of cellular therapies for solid cancers. Eligibility You must be a post-registration clinician and therefore must hold an MBChB degree or equivalent medical degree and ideally have a specialist post in a related subject, to apply for our Clinical Research Training Fellowships. It is generally expected that CRTFs will return to a training programme in the UK upon completion of their research degree. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University's Country Specific information page. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply Apply directly via this link: https://tinyurl.com/577zjazd or on the online application portal, select MCRC PhD Programme as the programme of study. You may only apply for one project within this scheme. Please ensure that your application includes all required supporting documents: Curriculum Vitae (CV) Supporting Statement Academic Certificates and Transcripts Incomplete or late applications will not be considered. Further details are available on our website: CRUK Manchester Centre PhD Training Scheme | Biology, Medicine and Health | University of Manchester Application Timeline Applications open: Monday, 5 October 2026 Application deadline: Monday, 23 November 2026 Interview date: Week commencing 11 January 2027 Start date: September 2027 Equality, diversity and inclusion are central to the University’s activities. The full statement can be found here: https://www.bmh.manchester.ac.uk/study/research/getting-started/equality-diversity-inclusion/”

Research areas