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1 November 2023
In the UK, more than 14,000 people are diagnosed with lymphoma each year. We interviewed Dr Alan Ramsay, a professor who works closely with this type of cancer to understand it more. We asked him about his work and how his research aims to help the 14,000 patients diagnosed each year.
Dr Ramsay is a Senior Academic at King’s College London, specifically researching lymphoma. Lymphoma is a type of cancer which arises in the patient lymph nodes. As a scientist Dr Alan Ramsay’s objective is to understand the biology of the disease, to understand how treatments work, and how treatments can be improved.
Dr Ramsay told us that as with so many people, his family was touched by cancer, so as a scientist, he was very motivated to work in cancer research.
“What attracts me to the field is that there is a real need for new therapies - for lymphoma and for all cancers. For lymphoma there have been a lot of advances in treatment, namely immunotherapy. Immunotherapy uses a patient’s immune cells to treat the cancer. I’m attracted to this work because I want to do what I can to advance that type of therapy”.
Dr Ramsay – can you tell us your research aims?
The first is to understand the biology of the disease. Lymphoma arises and grows in lymph node tissue. We're studying the impact of lymphoma on the cells within the lymph node. Through our research we have been drawn to these specialized cells called fibroblasts. Fibroblasts play an important role in how lymph nodes function, so we’ve been studying that. We want to understand the pathways that allow lymphoma to survive and progress. When we understand that biology, we will be able to think about ways of targeting the pathways or molecules that have gone wrong in the lymphoma tumour. That's a big aim.
The second aim is trying to understand how immunotherapy works, we do this by treating samples with immunotherapy. As part of this research we also need to understand how it doesn't work. Drug resistance is something that prevents many patients from benefitting from immunotherapy, so we need to understand why this happens and find ways to adapt. We want immunotherapy to work for more patients and for a much longer period of time. A cure is the best outcome but long term control is also desirable and that's something we are trying to achieve by studying in the laboratory here.
The third objective is to run more clinical trials, because this is how new drugs can get approved. We study samples from clinical trials to try and understand what did the tested drugs do to the tumour cells? What did they do to the immune cells? What can we learn?”
What motivates you?
Research takes a very long time, but I organise the research so we can try and discover relevant results sooner and think about new ways of treating lymphoma. The awareness that so many patients need better treatments motivates me. Being based in the hospital is also a natural incentive for me to do what I can to understand lymphoma better. Motivation is not the issue but it's the length of time it takes that is the biggest challenge.
What have been the results so far and how might the findings help patients?
We've just published an important study in the Journal of Clinical Investigation that's shown that lymphoma can change or corrupt cells within the lymph node. The results that we've published and that we're working on will hopefully tell us what are the signals or molecules that are promoting the survival of lymphoma. We hope they will also tell us what signals are stopping the immune system and immune cells from working properly, from detecting the cancer as being abnormal.
We want immune cells within patients to fight back and attack the lymphoma. One of our published findings showed that the fibroblast cells within the lymph node are suppressive towards immune cells - the T cells in patients. We discovered that the function of these cells is suppressive, and we have demonstrated that we can target these cells to prevent the suppression of immune cells.
Image shows: Targeted therapy enhances the formation of lytic immune synapses between CD8+ T cells and lymphoma tumor B cells. Granzyme B (white), F-actin (red), CLL cell (blue). This switch to revitalised T cell killing function can be augmented with novel CD20xCD3 T cell bispecific immunotherapy.
Hopefully our recent results will enable clinical trial testing of a new class of drugs which will attach to the fibroblast cells and prevent this suppression to the T cells. Our recent results could help us to identify a new way of treating lymphoma through a combination therapy. It also give encouragement to a new class of drug which has been approved in the USA and Europe, and hopefully will be approved in the UK as well.
Lymphoma is challenging disease in the sense that it's a cancer which affects the immune system, what we want to do is turn that around. I hope that by working with colleagues across KHP - clinicians and other scientists - we can get the immune system to fight back. That's the potential power of immunotherapy. We have very new ways of treating lymphoma, and our long term goal is to optimize these fully for patients.
I am grateful to the colleagues who have worked alongside me throughout this research. Piers Patten, King's College Hospital NHS Foundation Trust (NHS FT) and David Wrench, Guy’s and St Thomas’ NHS FT have worked with me throughout. All the academics at King’s College London, the core facilities at Guy’s and St Thomas’ NHS FT; people have really committed to helping us achieve our aims. I’m grateful to everybody, especially the patients who consent to trials and biobanking, which is essential to make sure that formal research is undertaken.
You can find out more about Dr Alan Ramsay’s research discoveries here - https://
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