Zebrafish reveal brain tumours’ secret ally

The immune system is designed to help and heal.

When foreign invaders attack, such as bacteria or viruses, it’s the job of specialised immune cells – called macrophages – to go to the site of danger and eat things that could cause us harm.

And they carry out this job in many different tissues around our bodies.

Even in the brain.

The immune system is carefully organised, with different macrophages assigned to patrol certain areas of the body, ready to raise the alarm if an intrusion occurs.

But when it comes to cancer, immune cells can put on a very different facade.

Glioblastoma is the most common type of brain tumour. But it’s also the most difficult to treat.

Survival has remained stubbornly low, with fewer than 5 per cent of people diagnosed with glioblastoma surviving their disease for at least 5 years.

The macrophages responsible for looking after the brain are called microglia.

But their response to brain tumour cells isn’t what you’d expect. Or hope for.

A new study from a team of our scientists in Edinburgh has made it possible to see the unexpected relationship that microglia have with brain tumour cells.

And their findings could open up a new way to test drugs for glioblastoma.

Blog: Zebrafish reveal brain tumours’ secret ally: https://t.co/UKT07RvDqQ pic.twitter.com/xbTwY7IC98

— Cancer Research UK (@CR_UK) October 28, 2016

Fluorescent fish and brain cancer

Dr Dirk Sieger, from the University of Edinburgh, has found a way to spy on the interaction between brain tumour cells and immune cells. And it involves working with transparent zebrafish.

His fluorescent microscope has produced eye-catching footage that reveals what happens when microglia and brain tumour cells first meet.

“You can actually see that the fish microglia, in green, really respond and go towards the tumour cells, in red.”

Microglia betrayal

It turns out that the brain’s microglia might encourage the tumours to grow, instead of destroying them.

“Looking at these interactions the microglia appear to be friendly towards the tumour,” says Sieger. “We call this ‘nursing’ as they really help and support the cancer cells develop.”

This immune deception may seem surprising, but macrophage betrayal seems to occur in almost every type of tumour.

But it seems the brain’s immune cells in question don’t just fraternise with any old cancer enemy.

Florescent fish and other cancers

Another video from the lab shows the immune cells reacting to a different type of cancer cell – called fibrosarcoma. This type of cancer isn’t a brain tumour, so these cells wouldn’t normally be found in the brain.

And Sieger and his team were surprised by what they saw.

The microglia respond strongly against these different tumour cells, and start engulfing them and breaking them down.

“The microglia are really cleaning up the strange tumour cells,” says Sieger.

And they’re hoping to turn this discovery into a new way to test experimental brain tumour drugs.

Testing new brain tumour drugs

Now Sieger and his team know what to look for when testing new immunotherapy drugs for brain tumours. And if a drug has shown promise in early lab tests, they could work with the zebrafish to help test it further.

If we can do this then the zebrafish will help us to understand how these immune cells can fight the tumour, and which drugs cause this behaviour

– Dr Dirk Sieger, Cancer Research UK

If the drug is effective in converting the microglia’s alliance, then the researchers will be able to see the microglia attacking tumour cells.

“This is what we’re aiming for,” says Sieger. “We can use these zebrafish to see if the drugs we have developed cause the same reaction.”

And it’s thanks to these tiny transparent zebrafish, small enough to swim under a microscope, that scientists can see what is going on inside a living brain tumour.

In the future, Sieger and his team hope to zoom in even further and decipher the ‘conversation’ between the cancer cells and microglia – something that can’t yet be achieved by simply studying cells growing in the lab.

They aim to discover exactly what the brain tumour cells are saying to the microglia to turn them to the dark side.

“If we can do this then the zebrafish will help us to understand how these immune cells can fight the tumour, and which drugs cause this behaviour,” says Sieger.

The hope is that our scientists will now be able to design drugs that could help the immune system redeem itself.

And, ultimately, turn its full force on brain tumours.

Gabi