MRC DiMeN Doctoral Training Partnership: Characterization of immunological responses in patients with liver cancer to predict immunotherapy efficacy and immune-related adverse events

Description

Liver cancer, a devastating and incurable cancer has poor patient outcomes largely due to late-stage diagnosis, limited treatment options, and lack of biomarkers for early detection and monitoring of disease progression and treatment response. Immunotherapies, such as checkpoint inhibitors (ICIs), that enhance an effective immune response have demonstrated robust anti-tumour efficacy in a subset of patients. However, the efficacy of such therapy varies, and, in some cases, may trigger a wide range of life-threatening immune-related adverse events (irAEs). Up to 40% patients receiving ICI therapies develop serious irAEs, which require cessation of therapy and immunosuppression that can compromise cancer treatment. The number of new cases and deaths from liver cancer could rise by 55% by 2040. With the increasingly widespread use of cancer immunotherapies, the cases of irAEs have become a prevalent and costly burden of immunotherapies in recent years, and likely will continue to increase with more complexity and severity, representing a major barrier to delivering effective immunotherapies to cancer patients. It is therefore important to identify predictive biomarkers that will discern which patients are most likely to respond to immunotherapy, as well as biomarkers that can monitor treatment response.

This multidisciplinary project aims to explore the comprehensive aspects of immune responses in liver cancer patients receiving ICIs and to develop a stratified clinical approach for predicting response and toxicity to ICIs for optimal cancer treatment. We will phenotype different immune cells present in blood and within a tumour tissue using mass cytometry. Tumour associated neoantigens presented by cancer cells or tumour tissue will be characterised using state-of-art Mass spectrometry methods. The function of tumour antigen-specific T cells will be assessed using immunological methods and tissue injury caused by cytotoxic T cells will also be evaluated. The data generated will enable us to understand how the immune system is responding to the tumour after the immunotherapy treatment. This could be key for identifying who can benefit from this treatment, as well as those who are at risk of experiencing serious adverse effects instead. By refining patient selection for immunotherapy more effectively, this would have a significant impact on the treatment of primary liver cancers, providing improved outcomes and quality of life for patients facing these challenging diseases.

The student will be based in the immunopharmacology group led by Prof Naisbitt (https://www.liverpool.ac.uk/people/dean-naisbitt,  X: @ImmunoPharm) and Dr Meng (https://www.liverpool.ac.uk/people/xiaoli-meng,  X: @xl_meng) at the Pharmacology department, University of Liverpool. The student will receive training in a wide variety of techniques including proteomics and advanced primary cell culturing. Under the supervision of Prof Palmer (https://www.liverpool.ac.uk/people/daniel-palmer ), the student will gain valuable experience in both clinical and translational medicine. An industrial placement at Apconix will also provide the student with opportunity to gain hands-on experience in immunotoxicity assessment within real-world drug development. Furthermore, this multi-disciplinary training will give the student a broad range of skills allowing a wide choice of career options post PhD, both within and outside of academia.

For informal enquiries about the project, please contact Dr Meng (xlmeng@Liverpool.ac.uk).

iCASE industrial partner web link: https://www.apconix.com/

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond. Further information on the programme and how to apply can be found on our website:

https://www.dimen.org.uk/