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The University of Southampton
Medicine

Cancer Sciences

immunology
Cancer cell

Cancer is having a massive global impact affecting millions of people and their families. At Southampton, we have a strong history of researching Cancer Sciences, from diagnosis to improving treatment and generating potential vaccines.

We are uniquely placed to bring together world-leading expertise across many areas of cancer research to battle against one of society’s most prevalent diseases

Last year, we opened the UK’s first Centre for Cancer Immunology where globally-recognised researchers are expanding clinical trials and developing more lifesaving drugs in the exciting and promising area of cancer research.

This pioneering Centre builds on our excellent existing infrastructure that includes the Cancer Research UK (CRUK) Clinical Centre, CRUK/National Institute for Health Research (NIHR) Experimental Cancer Medicine Centre, CRUK Clinical Trials Unit, NIHR Clinical Research Facility, Wessex Investigational Science Hub and a comprehensive NHS cancer treatment centre.

The aim of our interdisciplinary network is to apply basic science at the translational interface of cancer sciences, with a focus on cancer immunology and the tumour microenvironment. 

 Research areas:

Mechanisms in Adaptive Immunity

Focusing on the mechanisms of antigen processing and presentation, T cell activation and differentiation. Our research has helped to elucidate the basis of T cell epitope selection, and the structural characterisation of components of the antigen processing apparatus, resolving how these components determine the repertoire of peptides presented to the immune system. We have also provided new insight into the role of the TNF receptor superfamily on naïve, memory and exhausted T cells. These mechanistic studies have identified a number of potential strategies to enhance anti-tumour immunity and/or boost the efficacy of cancer vaccines.

B-cell malignancies

Focusing on the cellular and genetic mechanisms of malignant transformation in B-cells and translational research in the clinic. We are studying the mechanisms and targets that are downstream of the B-cell receptor (BCR) to identify novel therapeutic targets. This route has been enormously effective, with the development of new knowledge and trials using targeted agents such as PI-3 kinase and Bruton tyrosine kinase (BTK) inhibitors resulting in high response rates in low grade lymphomas. We also work to develop novel antibody therapeutics to B-cell targets such as anti-CD32 and anti-CD27; both reagents that were co-developed in Southampton and trailed through our links to Bloodwise and the CRUK New Agents Committee. With our considerable expertise in genomics and epigenetics, we have led or contributed to the discovery and characterisation of many of the novel DNA lesions emerging from recent high-throughput sequencing studies in these cancers.

Antibody therapeutics

This research is carried out by the Antibody and Vaccine Group and employs basic molecular and cellular biology, experimental model systems, and structural biology and chemistry to derive relationships between antibody structure and function, to aid in the development and optimisation of therapeutic approaches. We investigate all aspects of antibody biology, from new target identification, to engineering and biological mechanisms of action for direct targeting, immunostimulatory and checkpoint blocking reagents. It involves a large multi-disciplinary team of collaborators, which allows us to study antibodies and their targets from atomic resolution, through to signaling and cellular responses all the way to whole organisms. Southampton has particular international expertise in the area of Fc gamma receptor biology, using insights of isotype and Fc-manipulation to augment antibody function with a focus on targets of the TNF receptor super-family. The newly established Ward/Ober laboratory brings further expertise in antibody half-life extension, intracellular imaging and antibody-drug conjugates.

Translational Immunotherapy

An expansive programme of work that aims to catalogue the transcriptional profile of tumour infiltrating T-cells, linked to the antigenic, genomic and proteomic landscape of the tumour. This includes the development of microfluidic tools to permit the accurate analysis of the immunopeptidome. These approaches will help identify novel targets for cancer vaccine development. Via a CRUK Network Accelerator Award we are working with the Oxford CRUK Centre to apply microscaled methods to decipher the molecular architecture of immune responses directly in tumour tissue and allow their application in clinical practice. We are targeting the processes of tumour recognition in vivo, analysing the mutanome, transcriptome and immunopeptidome of three cancer types that are, in a proportion of cases, susceptible to immunotherapy: lung cancer, oesophageal cancer and melanoma.

Tumour microenvironment

Exploring the ecology of solid cancers with a focus on the biology of cancer-associated fibroblasts (CAFs) in head and neck, lung and oesophageal cancer. By understanding how CAF promote tumorigenesis and interact with other components of the tumour ecosystem across the treatment pathway, we identify the signaling pathways that might be targeted for treatment. Specifically, we work on ways of inhibiting the molecular phenotype of the CAFs, such as inhibitors of NOX4, that are now being explored in combination immunotherapy trials for head and neck cancer. We are comparing oesophageal CAFs and normal fibroblasts using single cell transcriptomics and proteomics to identify differentially expressed proteins in a range of pathways which might lead to novel approaches to therapy. We also characterise novel functional phenotypes using single cell RNA sequencing, mapping the spatial distribution of the cells in tissues using multiplexed image analysis developed through the CRUK Digital Pathology Accelerator. The oesophageal cancer group is part of the national OCCAMS collaboration, giving important insights into the genomic landscape of oesophageal adenocarcinoma and is leading efforts to establish predictors of response to neoadjuvant therapies. In collaboration with the Wellcome Trust Sanger Institute we have been able to establish a bank of oesophageal cancer organoids, and these are being combined with cancer-associated fibroblasts and immune cells for the study of single cell transcriptomes in a complex tumour model.

 

Breast Cancer

Brings together work on inherited and modifiable risk factors for breast cancer, to establish host factors that sway the outcome of primary breast cancer and inform primary and secondary prevention strategies. Building on our analysis of the effect of genetics on prognosis in more than 3,000 young onset breast cancer patients, we are now investigating the pathological and prognostic implications of lower penetrance breast cancer susceptibility genes and polygenic scores. Collaborations with immunological and bioinformatics teams are investigating the relationships between host genotypes and immunological responses to cancer. Collaborations with the Southampton Biomedical Research Centre Nutrition theme focus on body composition patterns and nutritional phenotypes, treatment toxicity and outcomes while a parallel workstream with academic psychiatry is focusing on health behaviour and cancer prevention interventions.

Surgery

The future of surgery for cancer is in combination with conventional and emerging anti-cancer therapies tailored to the patient and their tumour. As the leading surgical oncology centre in the south of England, we adopt a disease-wide approach from a sub-cellular level to population-based studies to deliver this agenda. Building upon our strengths in cellular interplay and the tumour micro-environment, and working with the Southampton NIHR BRC, we incorporate patient factors such as fitness and nutrition into complex models of risk prediction for cancer surgery.  Researchers from Southampton have delivered some of the most important clinical trials in surgical oncology in recent years, encompassing breast, colorectal, hepatobiliary and oesophageal cancers. The Cancer Research Theme’s basic and translation science portfolio in solid tumour biology is underpinned by extensive and comprehensive tissue collection across the treatment pathway, but especially during cancer surgery. 

Clinical Ethics and Law

Rapid technological advances promise big improvements in medical care, however, the world needs leadership in understanding and responding to the ethical and societal impact of these radical changes. In Clinical Ethics and Law, we bring together interdisciplinary expertise to meet this need by addressing the ethical, legal and societal issues through research, teaching, policy engagement and public dialogue. We consider what is needed to be ready to adapt, from the perspective of  the individual, as well as healthcare and society.

Much of our research focuses on the impact of recent developments in genetics and genomics and the complexities of delivering nuanced information to patients and public in the context of a deterministic public discourse.

Our Facilities

Edge

Delivering real-time data access for clinical trials management

WISH Laboratory

A bespoke laboratory providing translational research requiring quality assurance to regulatory standards

Tissue Bank

A valuable core resource to aid the study of cancer biology and associated research

Research Groups

 

Partnerships and collaborations 

Bioinvent

Celldex

 

 

Education opportunities

We welcome undergraduate and postgraduate students to our research theme. Southampton medical students can spend four months working in one of our research groups, as part their undergraduate studies. We also have several PhD programmes, including our Cancer Research UK clinical and non-clinical academic training programme. MRC DTP programme and newly established Immunology PhD programme. All of our programmes accept prospective PhD students onto the Faculty Integrated PhD programme.

Professor Tim Underwood

Professor Jonathan Strefford

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