Piecing together breast cancers’ immune cell composition

Surgery? Radiotherapy? Chemotherapy? A combination of two or perhaps all three? Doctors face a challenge when working out the best way to treat cancer patients.

Especially considering that 4 years ago our scientists redefined breast cancer as not one, but at least 10 different diseases.

The team found that patients’ tumours have distinct genetic profiles that define their disease. This went some way to explaining why some women with breast cancer fare better than others, but doctors are yet to find a reliable way to help predict outcome and tailor treatment for women.

And in the years that have followed, the picture has become even more complex.

As scientists have learnt more about the inner workings of different cancers, it has become clear that other cells are also found within tumours. And these too can change how a cancer behaves.

For example, immune cells are found in large numbers inside breast tumours. And their presence suggests they could be a prime target for immunotherapies that could turn these immune cells on tumour cells.

Now, Professor Carlos Caldas – whose team first discovered the 10 types of breast cancer – has found that the outlook for women with some types of breast cancer could be linked to the number, and type, of immune cells found within their tumours.

And their latest discovery – made at our Cambridge Institute and published in the journal PLOS Medicine – is one step towards doctors being able to better treat women with the disease.

An immune orchestra

Dr Raza Ali, a scientist in Caldas’s team, said their latest study has looked at how the immune system reacts to breast cancer in greater detail than ever before.

Previously the team counted the number of immune cells in breast tumours by looking at samples down a microscope. This is important, as it helps the researchers see where immune cells live within the tumour. But they can only look at a couple of immune cells at a time.

This is a challenge, because immune cells come together like an orchestra, and each type of immune cell has a different part to play.

Just listening to the violins and cellos in isolation won’t give you the whole picture of what the orchestra sounds like together. And the same is true of just looking for a couple of types of immune cell.

Now, using a technique that allowed them to look at 11,000 tumour samples, Caldas’s team has looked at more types of immune cells than ever before. The technique, called Cibersort, used genetic information to help scientists look at an ensemble of 22 different types of immune cells.

From this, they’ve been able to work out what the immune orchestra looks like in different types of breast cancer.

Finding the cancer’s tune

By looking at samples from different types of breast cancer, Caldas and his team uncovered a potential link between the immune cells that were present and how well women responded to chemotherapy.

They also believe that profiling the immune cell orchestra could offer information about survival. Their theory was that immune cells inside tumours come together to try to get rid of the cancer cells. So where women’s tumour samples contained a lot of immune cells, the team would expect those women to have had better outcomes.

The team found this idea held true for some women with a certain type of breast cancer (called ‘ER-negative’), but not for others.

In samples from the women with ‘ER-negative’ tumours – where the cancer cells stop making a key hormone-sensing molecule on their surface – those with the fewest immune cells within the tumour tended to have the poorest survival.

But around 2 in 3 breast tumours make too much of that hormone sensor, called the oestrogen receptor. And in these so-called ‘ER-positive’ breast tumours, the researchers heard a different immune tune. They found that having lots of a certain type of immune cell, called a monocyte, inside the tumour was linked with better survival. But having very few of a different type of immune cell, called an M0 macrophage, may also be beneficial.

Looking to the future

While these complex sounds are not easy to decode, Ali thinks the findings suggest that immune cells may influence how some breast cancers progress.

“The body clearly has a response to tumours, but how effective this is varies,” he explains.

“We need to understand the role the immune cells play in this response. This will help us predict which patients are at a high risk of their disease progressing, and if the immune cells change the way patients respond to treatment.”

One day these findings could help predict the outlook for women with breast cancer. They also raise the possibility of deploying one of the most talked-about treatments in recent years: immunotherapy.

Immunotherapies harness the power of the immune system by releasing the brakes on immune cells found in tumours. And Ali believes some breast cancer patients might also benefit from these immunotherapy drugs. Now researchers can start to work out if this is the case.

In fact, one clinical trial is underway to find out if giving a type of immunotherapy alongside chemotherapy could help patients with an advanced type of breast cancer.

But as Ali cautions, it’s still early days: “Immunotherapies, like all treatments, have side effects so we don’t want to be giving these drugs if they won’t work.

So no matter what the treatment, says Ali, “the biggest challenge now is to find a way that doctors can use this information to help find the best treatment for each woman.”