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Immune cells unexpectedly fight cancer

by Kat Arney | Analysis

9 May 2008

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Cancer Research UK scientists have found that certain immune cells – known as dendritic cells – may play an unexpected role in beating cancer.

A good idea – in principle

Our immune system protects us from attack by foreign invaders –the viruses and bacteria that surround us. But cancer starts from our own cells, which means the immune system usually fails to recognise or attack it.

Researchers are very interested in training the immune system to spot cancer cells and destroy them – this approach is known as immunotherapy.

One type of immunotherapy is based on dendritic cells, so called because they are covered with long ‘tentacles’ called dendrites. These cells are usually found in tissues that are exposed to the outside world, such as the skin, lungs, nose, stomach and guts.

Dendritic cells wander round our bodies, eating viruses and bacteria, then displaying fragments of them on their surface. Other immune cells ‘see’ these fragments, then make antibodies against them (special proteins that can recognise biological molecules), which they secrete into the bloodstream. The antibodies attach to the invading nasties, and so direct immune cells to attack them, getting rid of the infection.

For several years now, researchers have been working on ways to make a patient’s dendritic cells display fragments from his or her cancer cells. The idea is that this might help to train the immune system to spot cancer cells and destroy them. At the moment, most of this work is being done using animal models, although a few very small trials have taken place using cancer patients.

To do this, scientists purify dendritic cells from the blood of an animal or person with cancer, then expose them to proteins taken from its cancer cells. These dendritic cells are grown in the lab for a short time, then transplanted back into the animal or patient. Lots of scientists are working on this kind of technique, but so far there have been very few actual success stories.

Targeting breast cancer

Professor Joyce Taylor-Papadimitriou and Dr Joy Burchell run the Cancer Research UK Breast Biology Group at King’s College School of Medicine in London. They are studying the molecules found on the surface breast cancer cells, with the aim of developing immunotherapy approaches to target them.

As part of their work, they have been purifying dendritic cells from mouse bone marrow, then exposing them to a protein called MUC1, which is found in high levels in many breast cancers. The researchers then return these cells to the mice, inject them with breast cancer cells studded with MUC1, and look for an immune response to the tumour cells. Encouragingly, they found that these ‘treated’ dendritic cells could boost the immune response against cancer cells.

An unexpected result

As well as using treated dendritic cells, the researchers also used untreated, or ‘naïve’, cells as a control. This is an important aspect of all good experiments, to ensure that your results are due to the thing you’re testing, rather than something else in the experiment. But, amazingly, the researchers found that their naïve dendritic cells could also provoke an immune response against cancer.

In fact, injecting mice with naïve dendritic cells actually seemed to protect them from developing cancer when they were injected with tumour cells in the first place. The team found that the more dendritic cells they injected, the greater the protection. For example, they didn’t see a protective effect with 5,000 cells, but 50,000 or 500,000 was sufficient to provoke a response.

The researchers also tested a different tumour type, and although the dendritic cells didn’t completely prevent cancers from forming, they did slow down the growth of tumours. The team has just published their surprising results in the British Journal of Cancer.

But why?

The big question now is to find out why this is happening. The team showed that the dendritic cells stimulate the production of cytokines – molecules that can boost the immune system. This may be enough to trigger an immune response to the cancer. It may also be possible that dendritic cells may be picking up some cancer-related proteins when they’re grown in the lab, although the researchers used special growth broth to reduce the likelihood of this happening.

This finding obviously has big implications for research and clinical trials looking at immunotherapy – especially those that use untreated dendritic cells as a control. And this isn’t a unique observation. Intriguingly, another study has shown that naïve, untreated dendritic cells may have a protective effect against cancer.

Of course, much more research needs to be done into this fascinating phenomenon, but could we see cancer patients in the future being treated with dendritic cells to boost their immune systems? Watch this space.

There’s more about immunotherapy on the News and Resources website.

Kat