admin January 15, 2018

New immunotherapy discovery could give treatments the precision they need

Over the past few years, immunotherapies – treatments which harness the power of the immune system to fight cancer – have been making headlines around the world.

These powerful new weapons are exciting because once the immune system has ‘locked-on’ to a cancer cell it’s persistent and ruthless in taking it out. For patients in whom they work, immunotherapies can produce long-lasting effects. Some have even suggested they can cure certain cancers.

But the biggest challenges for immunotherapy have been identifying which molecules on the cancer cells are the best targets, as well as how to get past cancer’s defences.

For now, the immunotherapy treatments available to patients are powerful-but-blunt weapons, which in some cases can result in a number of potentially serious side effects.

What’s urgently needed are treatments that can guide immune cells to specifically attack a tumour, while leaving healthy cells alone.

And today, Cancer Research UK scientists have published a new study in the journal Science that may have uncovered the intelligence needed to precisely guide these new weapons.

But before we go into detail about what they found, and its implications for future research, let’s recap how different immunotherapies work.

Helping the immune system spot cancer

Over the years, researchers have tried many different approaches to turn the immune system against cancer, such as cutting the brakes on immune cellsflagging cancer cells for destruction, or genetically engineering a patient’s immune cells to directly target cancer cells.

But most of these depend on the immune system being able to recognise cancer cells as the true threat that they are. So how does this happen?

As we’ve written about before, almost all cells in our bodies display samples of the proteins they produce on their surface.

These small samples, called antigens, act as ‘flags’ for the immune system.

When a cell becomes damaged or infected, it changes the proteins it makes, displaying these as new antigens on its surface. Specialised immune cells, called T-cells, can then spot these antigens, releasing signals that destroy the damaged cell if the antigens aren’t looking the way they should.

The DNA faults inside cells that lead to cancer can also change how proteins ‘look’ to the immune system. So, theoretically, once the immune system recognises a cancer specific antigen, it should destroy all cancer cells that carry that flag. But this doesn’t always happen. And researchers have been working hard to find out exactly why.

Is recognition enough?

“Essentially there are two competing ideas”, says Dr Sergio Quezada, from University College London, and one of the world’s leading experts in how the immune system interacts with cancer.

If immune cells waste precious resources chasing after antigens that aren’tpresent on the surface of all the cancer cells then they risk missing parts of the tumour entirely

– Dr Sergio Quezada, Cancer Research UK

“One possibility is that the immune system simply needs to recognise cancer cells. Once it begins breaking open and killing tumour cells a domino effect takes place, allowing the immune system to recognise more and more ‘funny looking’ molecules.

“The other possibility is that the initial antigen that excites the immune system does matter. If immune cells waste precious resources chasing after antigens that aren’t present on the surface of all the cancer cells then they risk missing parts of the tumour entirely.”

Developing better immunotherapies is reliant on figuring out which of these ideas is true. But to answer this question would require an enormous amount of data from patients’ tumours.

Fortunately, another Cancer Research UK- funded team, working on a different challenge, have developed a set of tools that might help provide that answer.

An evolving solution

The Francis Crick Institute’s Professor Charlie Swanton is one of the world’s leading experts in the genetics behind how tumours grow and change, and the gene faults (mutations) that fuel this.

“One of the reasons why some cancers – lung cancer and melanoma in particular – are so hard to treat is because they evolve so rapidly they quickly outpace the drugs we use to stop them,” he says.

“These cancers have been exposed to many DNA damaging substances – such as cigarette smoke or UV light – and this damage gives rise to many different faults in their DNA.”

But as the data has poured in, Swanton’s team had begun to wonder whether this overwhelming complexity, which can make cancers so resistant to certain treatments, may be the very thing that reveals it to the immune system.

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