How a little known organ could protect people who’ve had stem cell transplants

In the build up to this year’s Stand Up To Cancer, we’re running a series of posts that focus on the science that is happening around the country thanks to your generous donations and amazing fundraising. The second in our series focuses on lymphoma and the immune system.

Professor Graham Anderson and Dr Beth Lucas, a postdoctoral researcher in his lab at The University of Birmingham, are studying how our immune system works.

They want to work out how one of our organs, the thymus, acts as a ‘training centre’ for a type of white blood cell by turning them into fully functioning immune cells. And their findings could help uncover new ways to protect cancer patients from infection.

In an unfortunate twist of fate, Beth was diagnosed with Hodgkin Lymphoma while studying for her PhD. So right now, the science she’s so passionate about may one day play a part in improving treatments for the disease she experienced.

We took a trip up to Birmingham to hear their story.

A molecular training facility for immune cells

During my treatment, it was nice to be able to come to the lab and just get on with things, and continue business as usual – Dr Lucas

If most people were asked to name a fundamentally important organ within our bodies that we wouldn’t survive without, they might say the heart, brain, or lungs.

But few would ever mention one of the most vital organs in our bodies – the thymus.

So what exactly is the thymus and why is it so critical?

“The thymus is an organ that sits above the heart in the chest,” explains Anderson.

“It acts as a ‘training facility’, where certain types of immune cells, called T-cells, mature and learn how to protect us.”

“T-cells do all kinds of jobs,” he adds. “They help to fight bacterial and viral infections, they help to target and fight cancer cells, and also help other immune cells to make antibodies.

“So they play a central role in our immune systems.”

T-cells are just one part of a huge fighting force. But all these cells come from just a single type of parent cell, called hematopoietic stem cells, which live in the bone marrow.

While the majority of these factory-like stem cells give rise to a diverse immune fighting force, a small group of immature cells are sent to the thymus.

Here they effectively finish their training, and complete their transition into a mature and functional T-cell.

A long journey before training begins

Although we know the T-cell’s journey to the thymus is far from straightforward, we know little about the details. This is where Anderson and Lucas’s research comes in.

“We’re trying to answer a very basic question,” says Anderson. “We want to know how the precursors of the T-cells get into the thymus.”

“They have to travel all the way from the bone marrow, so they have a long journey to complete. Once they get there, they still have to get access to the thymus ‘training facility’. But we know very little about how the access is granted.”

An image of the thymus captured on a fluorescence microscope.

Finding the key

The team has now discovered a molecule that acts as a special key to open the gates to the training facility.

“The molecule, called the lymphotoxin β receptor, seems to be a really important gatekeeper in controlling the entrance to the thymus,” explains Lucas. “In our experimental models, we’ve found that activating these ‘keys’ makes the gates open and more immature T-cells enter the thymus, ready to begin their training.”

So how does this link back to cancer?

The key to cancer treatments with fewer side effects?

Lucas is in remission from a type of cancer called Hodgkin Lymphoma. This, and other cancers such as myeloma and leukaemia, can happen because the cells that make up our immune system become faulty.

Her cancer has been controlled by chemotherapy. But sometimes this isn’t enough. So the next step is to have a stem cell transplant.

Our T-cells are the last blood cells to recover after a transplant and take longer to come back than the other immune cells – Professor Anderson

Here, a patient’s own stem cells and immune cells are destroyed using very intensive treatments, before healthy stem cells are put back in, ready to re-stock the body’s immune defences.

“We know that immune cells are particularly important after a stem cell transplant,” says Anderson. “But unfortunately, our T-cells are the last blood cells to recover after a transplant and take longer to come back than the other immune cells.

“The whole system is slow, but the T-cells are particularly sluggish. This makes people with these cancers more vulnerable to infection.”

But Anderson and Lucas think they might have a way to overcome this. They hope that by activating the lymphotoxin β receptor molecule to unlock the gates to the thymus, they can encourage more immature T-cells to begin their training.

“In our experiments, we have discovered that triggering the receptor around the time of the stem cell transplant boosts the number of immature T-cells entering the thymus,” says Lucas. “In essence, we can prop open the gates so the cells can get in quicker. And if they can get in quicker, they can get out quicker to do their work as a fully functioning T-cell.

“We’re just trying to speed things up and boost the immune systems of people with cancer,” she explains. “The quicker the immune system recovers, the better.”

This research is still in its very early stages in the lab. But both Anderson and Lucas hope that understanding these processes could pave the way for more research to find more effective treatments with fewer side effects in the future.

“If you think about the pipeline of research, we’re at the very beginning, trying to understand the mechanisms controlling the immune system that might then help better understand disease,” says Anderson. “Ultimately, this understanding could be passed along the pipeline and help to find new ways to treat and manage these diseases.”

Both a patient and a researcher

But did Lucas’s own cancer experience affect her research in the lab?

“I was involved in this research before my diagnosis, and having cancer hasn’t changed my approach to research,” she says. “I’m still as motivated and as interested as I was before. But because of my research mindset, I always want to find things out, so I was forever asking my doctor questions!”

“During my treatment, it was nice to be able to come to the lab and just get on with things, and continue business as usual,” she explains. “I was still able to do the science and wanted to carry on. And the team really supported me to do that.

“My treatment has been successful, and I’m now in complete remission.

“But I am aware that one day the cancer may return, and if this happens, I might need a stem cell transplant.

“So I can see first-hand how the research I’m doing might help people who need stem cell transplants in the future.”

Rebecca White is a research information manager at Cancer Research UK