The “humble” blood cells that could expose cancer’s secrets

Seven years ago, we brought scientists from all over the UK together to brainstorm ways of tracking down cancers using the clues they spill into the blood. One of those scientists, Professor Beth Psaila, turned the question on its head. She suggested investigating the way blood cleans itself up.  

Now, with our funding, Psaila’s team at the University of Oxford have found that tiny blood cells called platelets could help make cancer-detecting blood tests (liquid biopsies) much more effective.

If you’ve heard of platelets, it’s probably because of the role they play in blood clotting. They’re the bandages in the body’s inbuilt first aid kit, ready to rush in and expand to close any wounds – and they also work with white blood cells to detect and fight infections. Psaila’s team have shown there’s another side to that protective function. Platelets can use the same tricks to act like tiny sponges or hoovers, sucking up and storing any stray bits of DNA that get into the bloodstream.  

Crucially, that includes any DNA released by cancer cells – DNA that could help us find cancer earlier, when it’s more likely doctors can treat it successfully.  

“Our study shows that we can use blood in a different way to pick up on cancers at their very earliest stages,” says Psaila. “Studies looking for cancer hadn’t focused on platelets before, but we suspected that they may be informative because of their unique ability to hoover up things they encounter. They’re acting as sentinels in the blood.”  

Improving liquid biopsies  

Unlike traditional surgical biopsies, which work by taking samples directly from solid tumours, liquid biopsies can pick up signs of cancer from different parts of the body using fluids like blood or urine.  

That approach has big advantages, such as being less invasive for patients and providing information from across the whole tumour, not just the specific area that’s been biopsied.  

Liquid biopsies also have the potential to help doctors screen for and diagnose multiple different types of cancer before they start causing symptoms. In an ideal world, this could mean that more people can get the treatment they need sooner.   

But there are a few difficulties standing in the way.  

Blood-based liquid biopsies work by collecting and identifying minuscule fragments of DNA that cancer cells release into the bloodstream as they rapidly grow and die. Although most cancers release more of this cell-free DNA (cfDNA) than healthy cells, it’s still a very small amount. The early-stage cancers we most want to detect release even less.  

This drifting DNA can also cause other health problems, so the blood works hard to break it down and filter it out as quickly as it can – often before we can test it.

“One of the limiting factors for these tests is you don’t get enough of the important cell-free DNA that you’re looking for in early stages of cancer,” explains Psaila. “When the tumour is small, the amount of DNA it releases is very low, which makes these tests less helpful in the patients in whom screening is most important.”

That problem was already clear in 2018, when Psaila, now Professor of Haematology at the University of Oxford’s Weatherall Institute of Molecular Medicine, arrived at our liquid biopsy innovation sandpit. Liquid biopsies have come a long way since then, especially as tools for diagnosing symptomatic cancers and directing treatment. Still, the limitations mean there’s been less progress in using them to support earlier diagnosis and screening.

After the team’s discovery, that might be about to change.  

The secret life of platelets  

Psaila arrived at the innovation sandpit with a hunch that platelets might play a role in removing cfDNA from the blood. Even she’s surprised by how big that role has turned out to be. 

“We’ve shown that platelets hoover up cfDNA from multiple sources, including cancer cells,” Psaila explains. Remarkably, her team even found that they could use DNA in pregnant mums’ platelets to predict the sex of their babies.  

Platelets also seem to protect DNA from enzymes in the blood that would otherwise chop it up. That suggests the DNA in platelets may be much better preserved than the cfDNA today’s liquid biopsies look for in blood plasma. In that sense, platelets could be acting like tiny test tubes, preserving the crucial information that we need for our most sophisticated genomic tests.

“This is very early days, but clearly looking at platelets could increase the initial yield of DNA collected by liquid biopsies,” Psaila says. “It may even double.” 

With all that extra genetic information, liquid biopsies could pick up much earlier stage cancers. This study, which was led by Dr Lauren Murphy, a postdoctoral researcher in Psaila’s lab, even found platelets containing DNA from precancerous bowel cells, which had started changing in ways that might lead to cancer, but could still be stopped before they got there.  

So, platelets’ cancer-catching potential is clear. Future research will need to take a closer look at exactly how liquid biopsies that also analyse platelet DNA perform compared to current tools, but, after that, it could be relatively simple to put this unexpected finding into practice. 

“If it proves useful, then this approach could actually be translated very rapidly, because it’s just a small change in the initial processing of the blood sample,” Murphy says. “You wouldn’t need any other advances or technology, so rolling it out could be very straightforward.“ 

Blushing blood cells 

Still, platelets aren’t used to being the centre of attention. Despite everything her team has shown, Psaila still calls them “humble”. Because platelets don’t have any of their own DNA directing their behaviour, some scientists questioned Psaila’s focus on applying DNA testing techniques to them at all. 

“Platelets are the second most common type of cell in the body, but they’re also the smallest – and they don’t contain a nucleus. So there were some people who asked what on earth I was doing when we started analysing them for DNA,” Psaila says. “But whenever we spoke to actual platelet biologists, they were really fascinated. Lots of them had seen a little bit of a signal of DNA in platelets. Now we know that that signal points to something real.”

And while previous cancer research may have left platelets in the background, it’s becoming increasingly clear that actual cancers always kept them close. The reason platelets are especially good at collecting cancer DNA could well be linked to the fact cancer cells rely on them so much.

In fact, from the very earliest stages of cancer development, tumours press platelets into creating the blood vessels they need to get nutrients. Then, as they begin to move through the body, cancer cells coat themselves in platelets to shield themselves from the immune system. 

That close connection has helped cancers grow and spread for as long as they’ve existed. Now, finally, it might be a way to stop them.

Amal and Tim