(MCRC Clinical) Defining immune fitness in cancer: how cancer treatment and comorbidity shape systemic immunity

About the project

About the Project Cancer treatment is increasingly personalised according to tumour biology, yet the functional state of the host immune system is rarely measured. Patients enter the cancer pathway with different ages, comorbidities and immune histories, while surgery, radiotherapy and systemic therapies can each perturb immunity. These interventions are frequently combined or sequenced without systematic knowledge of their cumulative effects on immune competence. This PhD will define “immune fitness”: the capacity of the immune system to maintain effective, diverse and appropriately regulated responses and to recover following perturbation. Using serial blood samples and detailed clinical annotation from CAPTURE, a pan-cancer longitudinal cohort, the student will study immune fitness before, during and after cancer treatment. Three complementary blood-based readouts will be integrated. Antibody reactivity to common viruses will assess preservation of established immune memory. Reactivity to human endogenous retroviral antigens, particularly HERVK(HML2) envelope, will assess recognition of endogenous antigens associated with cancer and inflammation. Peripheral blood transcriptional signatures will quantify type I and type II interferon signalling, distinguishing transient immune activation from persistent inflammatory states. The project will determine: (1) how immune fitness varies at cancer diagnosis; (2) how surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy alter immune fitness over time, including the effects of treatment sequences; and (3) whether immune-fitness states and trajectories associate with response, toxicity and recovery. UK Biobank analyses of incident cancer will examine how age and comorbidity shape the pre-cancer host immune substrate. Key findings will be independently tested in MANIFEST, a national tumour-type-agnostic immunotherapy multiomic platform. The project will establish a framework for measuring immune resilience during cancer care, with the long-term aim of informing safer treatment selection and sequencing and identifying patients who may benefit from strategies to preserve or restore immune function. 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/”

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