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As we’ve mentioned before, there’s a stack of evidence that chronic inflammation – directed by white blood cells – plays a role in the development and spread of some types of cancer.

For a start, plenty of molecular studies have found that the chemicals involved in controlling inflammation also seem to be involved in cancer.

Secondly, population studies have linked conditions like Crohn’s disease, asbestosis, H. pylori infection, and hepatitis all have a link to cancer.  In addition, people who regularly take anti-inflammatory drugs like aspirin have a reduced risk of the disease.

And crucially in this story, studies of cancer samples have revealed that tumours are studded with white blood cells that are known to be involved in inflammation. It now seems that the more white cells there are in a patient’s tumour, the more likely the cancer is to spread, and the worse the patient’s outlook.

But white blood cells are supposed to be the good guys – the body’s policemen. Could they also be aiding and abetting cancer spread? To try to find out, US researcher Professor Lisa Coussens has been studying the role of white blood cells in cancer for over a decade.

Her lab at the University of California, San Francisco, have found that certain specific types of white blood cell seem to shift from playing ‘good cop’ to playing ‘bad cop’ inside tumours, helping cancer cells escape like a corrupt sheriff might let a killer out of jail.

 Different types of white blood cells

The immune systems is complex.  In the same way that a police force has detectives, beat cops and forensics experts, there are many of different types of white blood cell. Broad groups like B-cells, T-cells, neutrophils and macrophages can be further categorised into subgroups, depending on the proteins they carry on their surface – which in turn depends on what the cells are actually up to.

And over a white cell’s lifetime, circumstances can cause it to flip from one subgroup to another, changing its internal chemistry as it goes. It’s a hugely complicated and dynamic system, which scientists are slowly beginning to understand.

So, in trying to understand the role of white blood cells in breast tumours, Professor Coussens’s lab started by asking which exact types of cells are present, how they are dependent on each other, and which ones are key for cancer spread.

T-cells and macrophages

The team carried out a series of experiments that pinned the blame firmly on two types of white blood cell.

The first to be fingered were macrophages. These play an important role in many immune processes, both by absorbing and digesting foreign particles, and by releasing cocktail of chemicals that can affect the functions of other cells – this latter function is their main role in inflammation.

The second white blood cell they found at the ‘crime scene’ was a type of T-cell called a “helper” T-cell.

Helper T-cells seem essential for cancer spread

Next, using genetically modified mice, the team showed that removing helper T-cells from breast tumours dramatically reduced the ability of cancer to spread to the lungs. And when helper T-cells were injected back into the mice, the cancer started to spread. No other cell type they studied had this effect.

They also discovered that removing helper cells had a big effect on the type of macrophage found in the cancer.

A bit of background

Decades of studies of immunology have found that helper T-cells are the immune system’s ‘chief commissioners’ – producing chemicals called cytokines that change how other white blood cells behave, and directing the immune response depending on the body’s needs.

Helper cells have two ‘modes’ of cytokine production – one, TH1, tells nearby white cells to attack bacteria and other foreign invaders. The other, TH2, occurs during inflammation, and encourages other cells to divide and spread.

So Professor Coussens figured that the helper cells were releasing something that affected macrophages in the breast tumour, and this was causing cancer spread.

Detective work

Another series of clever experiments, on mice, and on cells grown in the lab, revealed the chain of events.

Helper T-cells inside tumours somehow get stuck in ‘bad cop’ TH2 mode, and release a chemical called IL-4.

This causes macrophages to migrate through the body to the tumour, where they release another chemical called EGF. This in turn causes cancer cells to become mobile and spread.

Blocking these events – perhaps by finding a way to flip the helper cells back to ‘good cop’ mode, could be a way to stop breast cancer from spreading.

All this may seem like a complicated chain of events, but understanding this sort of stuff is absolutely key to developing new cancer treatments. Cancer that stays confined to the place where it started is relatively easy to treat – once it has spread, it’s much harder.

Finding ways to block this process is essential.  Breast cancer survival rates are on the increase, but there’s still work to be done to bring these figures down further, particularly for the minority of women for whom current treatments don’t work.

Professor Coussens is now trying to understand how these processes fit together in cancer patients, and which step in the chain – if any – is the best one to target with new treatments.

Henry

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