Dr Stephanie Burnell

I am supported by the Wales Cancer Research Centre and the Wales Cancer bank 

I work with patients undergoing colorectal cancer surgery who donate their tissue to research. The tissue that I collect is then processed in the lab and developed into organoids, also known as 3D “mini organs”. Organoids recapitulate multiple aspects of real organs, making them promising models of organ development, function and disease. The 3D structure offers increased complexity when compared to cell lines and presents numerous opportunities for drug development; from determining the efficacy of new drugs or treatments to the exploration of how the immune system might recognise, isolate and kill malignant but not healthy cells.

Lorenzo Capitani

Colorectal cancer (CRC) is the third most common cancer - despite advances in treatments, advanced forms of the disease still carry an unfavourable prognosis for patients. Currently existing immunotherapies have shown variable efficacy in CRC, with some subgroups of patients deriving no benefits. It is clear that it will be necessary to target other immune receptors that are driving immune suppression in CRC if we are to improve the outcome of patients.

LAG3 is a negative regulator of immune responses which is being investigated in an ever-increasing number of clinical trials. In CRC, LAG3 expression on T cells is associated with a poor prognosis and the lab has previously shown an enrichment of LAG3+ subset of regulatory T cells in CRC tumour samples. The aim of my PhD therefore is to contribute towards a better understanding of the role of LAG3 in the tumour micro-environment through the use of in-vitro model systems (including organoids) to test a range of LAG3 targeting immunotherapies. A better understanding of LAG3 function will hopefully enable and facilitate the development of rationalised LAG3-based immunotherapies for CRC and other cancers.

Link to video explaining Cancer immunotherapy can be found here and game developed to understand T-killer: harness the power of the immune system can be found here

Dr Hannah Reed and Jess Oliver

Working with our clinical colleagues at Velindre Cancer Hospital (Drs Tom Rackley and Catherine Pembroke), our research aims to develop a stronger understanding of the effect of ablative radiotherapy on immune cells in the blood of patients with oligometastatic and primary cancer. Collecting longitudinal blood samples from patients undergoing radiotherapy, we look for changes in T-cell phenotype and function of T-cells. By understanding the dynamic effect of radiotherapy on immune cells, we hope to identify the best timing for combining radiotherapy with immunotherapy drugs. 

Jess is also collaborating with Prof Tony Purcell at Monash to look at how radiation affects the immunopeptidome and how this may impact T cell responses.

Dr Bruce MacLachlan

My research focuses on how the immune system recognises cancer with the aim of harnessing this knowledge to design improved cancer vaccines. I utilise structural and molecular immunology techniques to understand the way in which antigen presenting cells display cancer antigens as peptides to T cells on the HLA-II system. Using these techniques, we can understand which peptides are presented to CD4+ T cells and try to decipher why specific peptide epitopes are immunogenic to the immune system. Consequently, using this structural knowledge, I work closely with The Gallimore Godkin Cancer Immunology Lab to find new ways to make HLA-II presented cancer antigen peptides more immunogenic to CD4+ T cells. My work is funded by a Health and Care Research Wales – Health Research Fellowship which supports me to drive my own research through collaborating with research teams in Cardiff and further afield.

Dr Martin Scurr

Dr Scurr’s research investigates the phenotype and function of T cells, with a particular focus on analysing tumour-specific T cell responses in colorectal cancer (CRC) patients. His work uncovered the suppressive effects of certain populations of tumour infiltrating T cells on other anti-cancer T cells, leading to the design and implementation of the phase I/II clinical trial, TaCTiCC, testing a novel immunotherapeutic combination in advanced CRC patients. 

In addition to this, Dr Scurr has led two MRC-Proximity to Discovery: Industry engagement grants, developing successful academic-industry collaborations that generated novel treatments and methods to analyse immune responses. He is also a prior recipient of the Future Leaders in Cancer Research (FLiCR) grant.

Dr Scurr is also the co-founder and chief scientific officer of ImmunoServ Ltd. (www.immunoserv.com), a Cardiff-based contract research organisation specialising in the immunology sector, with its own R&D pipeline for developing a range of tests that measure immune responses to viruses, bacteria and cancer. He is the lead investigator on an SBRI-Innovate UK-funded project to develop COVID-19 antibody and T cell tests for population-scale immunity screens. This work resulted in several high-profile publications detailing the importance of measuring adaptive immune responses to SARS-CoV-2, particularly in immunocompromised individuals; the test is now being used clinically to manage at-risk patient groups.

Dr Stefan Milutinovic

The ability to comprehensively map heterogeneity in any given tissue is often hindered by limited sampling and interobserver variability which arises from staining and analyzing thin tissue sections. The ability to obtain a comprehensive global overview of microstructures in whole tissues deemed too large for conventional microscopy has however been made possible with developments in tissue clearing as well as the use of mesoscopic imaging techniques such as light sheet fluorescence microscopy (LSFM).

I employ LSFM imaging to better understand how specialised blood vessels termed high endothelial venules (HEVs) are altered in tumour draining lymph nodes following tumour establishment as well as how these networks change in response to immunotherapy using computational tools which enable the topological mapping and extraction of numerical descriptors of HEV networks.

The presence of HEVs in tumours has been linked to enhanced lymphocyte infiltration and favourable clinical responses. I have applied a similar approach to characterize the development of HEVs in tumours and how these change in response to T-cell based immunotherapies. Results from these findings can be found here