Hypoxia-driven macrophage modulation in cancer and its impact on T cell immunotherapy

Hypoxia is a common feature of solid tumours. It presents a significant challenge to effective cancer treatment using immunotherapy.

Macrophages are known to be recruited to hypoxic regions of the tumour and undergo polarisation to an M2 pro-tumorigenic phenotype. This phenotypic shift can substantially impact the efficacy of T cell immunotherapy.

The aim of this PhD project is to evaluate the role of hypoxia in modulating macrophage function during tumour progression. Cutting-edge platforms for single-cell and whole-body imaging, immuno-profiling and transcriptomic analysis will be employed to examine the spatial and dynamic changes in tumour hypoxia, macrophage function and their interactions with T cells within hypoxic niches.

Tumour spheroid models and preclinical immuno-oncology mouse models will be established to evaluate these mechanisms. Treatment strategies will be developed to target hypoxia and macrophage-mediated immunosuppression in cancer.

Supervisor's interests

Immunotherapy has revolutionised cancer treatment. Various interventions such as immune checkpoint inhibitors, cancer vaccines and engineered chimeric antigen receptor T cells, have been developed over the years to enhance anti-tumour immunity.

Despite the increasing adoption of immunotherapy in routine clinical practice, only a minority of patients benefit from treatment, and autoimmune side effects may occur in some patients on systemic therapy.

Several factors like immunogenetics, cancer types and stages, and underlying tumour immunobiology, play a crucial role in determining response to immunotherapy. There is a need to understand the mechanisms involved in anti-tumour immunity and treatment resistance to improve the outcome of immunotherapy.

How to apply

If you are interested in applying for the above PhD topic please follow the steps below:

  1. Contact the supervisor by email or phone to discuss your interest and find out if you would be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
  2. Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
  3. Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

Good luck!

This is a self funded topic

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.

Meet the Supervisor(s)

Doreen Lau - Dr Doreen Lau is a Lecturer at Brunel University of London and a Visiting Researcher at the University of Cambridge. She began her scientific career at the Agency for Science, Technology and Research (A*STAR) in Singapore, where she focused on functional genomics and imaging in developmental biology. She later earned her PhD at the University of Cambridge as a Cancer Research UK and Cambridge Trust Scholar under the co-supervision of Professor Ferdia Gallagher and Professor Klaus Okkenhaug, specialising in cancer immunology and the clinical translation of molecular imaging biomarkers for cancer immunotherapy in both patients and preclinical models. Dr Lau has a broad interdisciplinary background spanning cancer immunology, pharmacology, and biomedical imaging. She trained in cancer imaging and pharmacology at Imperial College London under the guidance of Professor Eric Aboagye, worked at the University of Oxford on antigen presentation in cancer with Professor Tim Elliott, and served as a Visiting Scientist at AstraZeneca, where she developed tissue-based imaging biomarkers in immuno-oncology. She has contributed to teaching, previously serving as a part-time lecturer at the University of Oxford, where she co-led the Cancer Immunology module and lectured on imaging, disease mechanisms, and cancer treatment on MSc courses. Her research contributions to cancer immunology and imaging have been recognised with multiple international awards, including the 1st Place William G. Negendank Young Investigator Award in Cancer Imaging (ISMRM, 2018), the Women in Molecular Imaging Network Scholar Award (WMIS, 2019), a Top 3 PhD Award (ESMI, 2021), the Merit Travel Grant and Best Poster Award in Immuno-Oncology Biomarker Development (ESMO, 2023), and the Best Flash Talk in Cancer Immunology (CAMS-Oxford Institute, 2023). In recognition of her achievements as an early-career scientist, she was also elected to a Junior Research Fellowship in Sciences at Wolfson College, University of Oxford, in 2022.