Where does your interest in cancer immunology stem from?
My PhD (in 2001) was in transplantation immunology. I was researching the way in which your immune system recognises a transplanted organ, in order to find new therapies to prevent rejection. I was investigating ways to induce tolerance through manipulating the immune response. With cancer, it is almost the opposite end of the spectrum. Rather than trying to stop an immune response, you are trying to get it going. But if you can understand the mechanisms behind how and why to switch it off, you can also understand how to switch it on. My postdoctoral research helped me understand these fundamentals and showed me the potential – how we might be able to exploit the immune system, to switch it on, to kill cancer cells. Working in Southampton appealed because of the reputation of the world-leading research in cancer immunology, in particular in the labs of Professors Tim Elliott and Martin Glennie.
What is your area of research at the moment?
We have a really good idea now that your immune response plays an important role in identifying cancer. However, the cancer starts mutating and changing the way it looks to the immune response. My research looks at how these changes occur. Normally cells display “flags” on their surface which communicate what’s going on inside the cell. Any changes, such as if the cell is infected with a virus or has mutated into a cancer, are detected by the immune response, in particular killer T cells that look at the flags to see if everything is normal. If things have changed the killer T cells will identify these cells and kill them. Cancer cells can evade the immune response by reducing the number of flags, which makes the message weaker and confusing the immune system, or by changing the way the flag looks, in order that the immune system doesn’t understand the message. My work is to try to understand how the cancer cell is changing those flags and what it looks like from the surface. We have a good idea how it is changing things. Our challenge now is to try and reverse that process.
What success is immunotherapy having?
Clinical trials of drugs for advanced and terminal cancers, including melanoma (skin) cancer are showing incredible results. There are patients surviving stage four illness, and large tumours shrinking to nothing. It is early days and only happening in 20-40 per cent of cases, but late stage melanoma is historically an incredibly difficult cancer to treat and the survival rates are very low. Getting 20-40 per cent surviving in this cohort is massive, a huge impact. The next stage is to understand why the therapy is working and also why it isn’t working in certain people. This will give us important information about treating these cancers and help us discover just how beneficial they will be.
How does your work tie in with other ongoing cancer research?
I have a team of seven people. We are taking one angle in terms of how we might be able to utilise the immune response to fight cancer. Others are taking slightly different avenues. They are looking at antibody therapies that target particular molecules on the cancer cells to highlight them to the immune system and also checkpoint inhibitor drugs that release the brakes on T cells to allow them to target and kill the cancer cells.
We are a small spoke in a large wheel, and we are fighting this on many different fronts. We have more than 100 researchers, clinicians and associated staff.
What drives you in your research?
I have always had a natural curiosity to work out how things work and why. As a child I was never satisfied with the answers I was given. It was always “why, why, why?” I was drawn to this area of research as I wanted to know why the immune response works too well in some respects and then not well enough in others. Why it is that the immune system has gone wrong?
I still have that curiosity. I love what I do, because every day is new, finding out things that no-one has found before. I can’t imagine having done anything else.
How do you relax?
I play sport, particularly football. I also spend time with my family. I am constantly thinking at work, which can become a bit obsessive, so I try and have downtime. Sport is good in that it is more instinctive and frees your mind up.
Do you like talking about work?
I think communicating what we do is really important. There is a large disconnect between what the general public understand and what we know, and it’s much better that they have a grasp on what we do, how and why. It’s also good for people in Southampton to know that we have got a world-class centre that they can be proud of. And finally it’s good to invigorate kids, to let them know that it is OK to do science, particularly children from less privileged backgrounds. People are just as curious wherever they are from.
What does the future hold?
We are in an amazing golden period thanks to immunotherapy. We have the technology and the ability to manipulate things. Before we had a sledgehammer (with chemotherapy) and now we have a screwdriver to be more precise. There is huge potential. We can see the fruit and we want to pick it!
Cancer will probably always be with us, as there are lots of different ways that it can arise. But for certain types of cancer, in particular when the immune system is involved, I can see a day when we will either have a vaccine or we will have effective treatments. Eventually, we believe immunotherapy has the potential to treat over 100 different types of cancer.
How will creating the Centre for Cancer Immunology at Southampton help?
If we pull each of these research areas together, we could start to map out a much more cohesive framework, understanding not only what we see, but also informing what we want to do in the future. We will be able to forge more unique ways of looking at things. On top of that, we will attract world-leading scientists and will be able to speed up our research tremendously.
Thanks to the ongoing work of our cancer immunology specialists, an estimated 20 per cent of our clinical trial patients are living cancer free. With the new Centre, we will accelerate our progress and save more lives from cancer. Find out more about the campaign and how you can support it at southampton.ac.uk/youreit