Lung cancer cells. Credit: LRI EM Unit

Our Science Surgery series answers your cancer science questions.

Sara asked: ‘Why do some cancers metastasise but others don’t, even if they’re present in the body for many years?’

“We have so many unanswered questions about how and why cancer spreads around the body,” says Dr Seth Coffelt, an expert in the immune system and cancer spread (metastasis) at the Cancer Research UK Beatson Institute in Glasgow. “But one thing we do know is that not all cancers seem to metastasise, and some do it faster than others.”

These differences are especially apparent in skin cancer. On the one hand you have a type of non-melanoma skin cancer called basal cell skin cancer. This is the most common form of skin cancer, but it hardly ever spreads. On the other hand, a rarer form of skin cancer called melanoma often spreads, unless it can be treated in time.

“When we say cancer has metastasised, what we mean is that cells from a tumour in one part of the body, such as the breast, lung or bowel, have escaped into the bloodstream and travelled to a different part of the body and started to grow into a new secondary tumour there.”

Coffelt says these secondary cancers often grow in predictable sites, such as the brain, bones or liver, depending on the type of cancer in question.

And where cancer settles isn’t the only thing that differs between cancer types. “Something we’re learning, for example in breast cancer, is that metastasis happens at different rates. In one type of breast cancer, recurrence is most likely in the first 5 years. But in another type, the risk persists 20 years after patients were diagnosed and treated.”

Read more: the scientists working to predict how and when breast cancer returns to help personalise treatment plans.

The problem with metastasis

Although the speed of this process differs from one cancer to another, in general the later the cancer is diagnosed, the more time it has had to spread.

“This is bad news for the body,” says Coffelt. “Cancer cells that have escaped from the first tumour can be more resistant to cancer drugs and there can be more than one, or even several secondary tumours. So metastatic cancer is harder to treat.”

For patients with bowel cancer that’s spread, also referred to by doctors as stage 4 cancer, the likelihood of someone surviving their cancer for at least 5 years is less than 1 in 5, compared with more than 9 in 10 if diagnosed at the earliest stage. This is a key reason why we’re investing in research to detect cancer early, as well working with government to get more cancers diagnosed at an early stage.

But scientists are also interested in understanding how cancer spreads. Coffelt says there are several steps that have to happen to allow cancer to move around the body and establish a new tumour.

“The cancer cells need to leave the primary tumour, they have to survive the journey without being spotted by the immune system and then they have to be able to grow in a different environment,” says Coffelt.

“My research looks at one important step in this process: how the immune system gets switched off, specifically at the sites of metastasis.”

Tricked into helping

Coffelt is investigating how one type of immune cell in particular can either help or hinder cancer’s spread.

“Cancer couldn’t spread around the body without help. Looking at breast cancer cells, we’ve discovered that they can get some help by manipulating a particular type of immune cell, called gamma delta T cells.”

Gamma delta T cells are just one of several different types of immune cells know as T cells, which circulate in our bodies and protect us from disease. What makes gamma delta T cells unique is their ability to tell other T cells what to do. Under their instructions, other T cells in the bloodstream can either attack cancer cells or let them go free.

“Gamma delta T cells orchestrate this key process,” says Coffelt. Even when these immune cells are sitting in other parts of the body, they’re still able to pick up signals being produced by cancer cells. They take these signals and release their own messages that in turn switch off killer immune cells in the blood.

“It’s like a long-distance insidious communication system.” And this series of signals helps to give cancer cells protection as they move around the body.

“Cancer cells are heading out into the body and this signalling means they don’t have to worry about coming under attack, they can avoid being killed and land wherever they want to land.”

Taking on a new challenge

Coffelt and his team are now investigating if this communication system exists in other types of cancer too, in particular pancreatic cancer.

The odds of surviving pancreatic cancer are low compared to other types of the disease and a key reason for this is that more than half of patients are diagnosed when the cancer has already spread to other parts of the body.

“If we’re trying to understand why some cancers metastasise but others don’t, pancreatic cancer is an important but challenging area to work on. Fortunately here at the Beatson, we already have a team of researchers with expertise in how pancreatic cancer grows and develops.”

Getting the immune system back on side

Figuring out why some cancers spread is vital, but it’s not the ultimate goal.

As Coffelt’s research suggests, our body’s immune cells have the potential both to protect us from disease, but also to be tricked into helping cancer grow and spread. Boosting the positive traits of these cells or halting their negative influence to fight cancer is a job for treatments known as immunotherapies.

This is not only an exciting area of research for many of our scientists, it’s also starting to make its way into the clinic for treating some types of cancer. And Coffelt thinks immunotherapy might be a useful strategy to help stop cancer spread.

“We are trying to understand this T cell signalling process better and how to reverse it, because that could ultimately form the basis for a new type of cancer treatment.”

Coffelt believes that tackling metastasis in this way could have wide-ranging benefits. He says that once a cancer starts to spread, it can move to lots of different sites around the body. “Once this happens, we don’t have many treatment options to stop the cancer moving around.” Something that Coffelt is working to change.

“Our research might stop cancer from metastasising in patients with early stage disease, but it might also help us find a way to treat patients whose cancer has already spread.”

Kerry Noble is a freelance science writer