CAMS-COI, NDM Research Building, Old Road Campus, Oxford, OX3 7FZ
Oxford University Hospitals NHS Foundation Trust
BM BCh, MA (Oxon), D.Phil, MRCP (UK)
Clinical Career Development Fellow in Renal Medicine
- Post-CCT Fellow in Renal and Acute (General) Medicine
Using immunological biomarkers to improve outcomes for organ transplant recipients
A transplant is the most effective treatment for advanced kidney disease. As a result, we are transplanting more and more people each year. Because kidney disease is most common in older people, the average age of transplant recipients is increasing. Advances in recent years have significantly improved the short-term outcome of patients who receive a transplant, but long-term outcomes remain modest. This is partly due to the medication that must be given to prevent the immune system attacking the transplant (‘immunosuppression’). Over time, this medication damages the transplant and makes patients more prone to infection and cancer.
My research focuses using markers in the immune system to identify patients who may be at risk of complications after a renal transplant. I am particularly focused on exploring the effect of ageing in the immune system on transplant outcomes. As we age the immune system undergoes several changes through long-term exposure to viruses and other factors in the environment. We refer to these changes as ‘immunosenescence’ (immune ageing). Over time, this can lead to the immune system being less effective at protecting us from infection and less responsive to vaccination.
My doctoral work, supervised by Professor Kathryn Wood in the Transplant Research Immunology Group in the Nuffield Department of Surgical Sciences, demonstrated that patients with a long-term kidney transplant who shows signs of immunosenescence are more likely to develop skin cancer (Bottomley et al, J Am Soc Nephrol, 2016). Since then, we’ve focussed on what is happening in the skin itself as immune ageing develops, identifying changes in pathways that are key to mounting an immune response to cancer (Bottomley et al, Int J Mol Sci, 2019).
Our current work focuses on changes that occur within the immune cells present in the skin prior to the development of skin cancer; specifically we are interested in the impact of immune ageing combined with the use of immunosuppression after transplantation.
The work we are undertaking in this area may allow us to use the immune system in clinical practice in the future, to guide the type and amount of immunosuppression we give to transplant recipients. Being able to identify patients who may safely take less immunosuppression may reduce the problems encountered by patients partly as a result of these drugs, including cancer and infection. Furthermore, our work may identify new pathways that can be manipulated to encourage the immune system to fight off cancerous cells. Drugs that suppress the immune system are used in many other conditions, such as in autoimmune conditions, and our findings have relevance to these populations too.
My research has been generously funded by the Wellcome Trust, British Skin Foundation, Oxford Hospitals Charity, University of Oxford and the Chinese Academy of Medical Sciences.
Alongside my research, I am a practicing physician, qualified in nephrology and acute general medicine, and work clinically in the Oxford Kidney Unit at the Churchill Hospital.
Dampened Inflammatory Signalling and Myeloid-Derived Suppressor-Like Cell Accumulation Reduces Circulating Monocytic HLA-DR Density and May Associate With Malignancy Risk in Long-Term Renal Transplant Recipients
Bottomley MJ. et al, (2022), Frontiers in Immunology, 13
The COVID-19 Pandemic Is Associated with Reduced Survival after Pancreatic Ductal Adenocarcinoma Diagnosis: A Single-Centre Retrospective Analysis
Madge O. et al, (2022), Journal of Clinical Medicine, 11, 2574 - 2574
Transplantation Without Overimmunosuppression (TWO) study protocol: a phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients.
Brook MO. et al, (2022), BMJ Open, 12
Dampened inflammatory signalling and myeloid-derived suppressor-like cell accumulation reduces circulating monocytic HLA-DR density and associates with malignancy risk in long-term renal transplant recipients
Bottomley MJ. et al, (2022)
DONOR CYTOMEGALOVIRUS SEROPOSITIVITY CLUSTERS WITH RISK FACTORS FOR DELAYED GRAFT FUNCTION IN RENAL TRANSPLANTATION, BUT DOES NOT DIRECTLY CONTRIBUTE
Dumbill R. et al, (2021), TRANSPLANT INTERNATIONAL, 34, 189 - 189
OUTCOMES OF AKI IN RENAL TRANSPLANT RECIPIENTS WITH COVID-19 INFECTION: A TRAINEE-LED, MULTICENTRE, INTERNATIONAL REGISTRY STUDY
Bottomley M. et al, (2021), TRANSPLANT INTERNATIONAL, 34, 396 - 396
CD8+T CELL SENESCENCE IS A DISTINCT IMMUNOLOGICAL STATE THAT IDENTIFIES LONG-TERM RENAL TRANSPLANT RECIPIENTS AT INCREASED RISK OF FUTURE MALIGNANCY
Bottomley MJ. et al, (2020), TRANSPLANTATION, 104, S106 - S106