Wednesday, April 30, 2014
Cancer uses a three-phase strategy to trick your immune system
Cancer uses a three-phase strategy to trick your immune system (Source: IvonneW/iStockphoto)
Last time, I told the story of Daniel, a young man dying of widespread malignant melanoma. His doctor blasted one of the secondary melanomas inside his hip with a high dose of radiation, specifically to relieve the pain inside his hip.
Daniel was incredibly lucky. Somehow (and we still don't know how) that radiation dose to his hip 'caused' all of the widespread malignant melanomas scattered throughout his body to shrivel up and die. This is the very, very, rare abscopal effect. Fourteen years later, Daniel is still alive and well.
But first, exactly what is a cancer?
Let me start with the several hundred different types of cells in your body — liver, lung, spleen, muscle and so on. They grow. They all follow the general rule that they grow to a certain point — and no further. Then they stop growing. But when something goes wrong with this process of cell growth, it no longer follows that rule. Instead, that single cell will keep on growing, invading local tissues and perhaps spreading to distant parts of the body. It has become a cancer. By the time it has divided about 30 times, it will have generated about one billion cells and reached a mass of about one gram. At this stage, it is just clinically detectable.
In the year 2007, cancer killed nearly eight million people, worldwide. In other words, various cancers accounted for about 13 per cent of all human deaths.
The causes of cancers are many and varied — but surprisingly, only about five to 10 per cent are inherited. Diet, obesity and lack of exercise caused about 30 to 35 per cent of cancer deaths, followed by tobacco killing 25 to 30 per cent, infections at 15 to 20 per cent, and ionising radiation up to about 10 per cent.
Cancers are not completely 'invisible' to your immune system, but they may as well be — because of their beautifully evolved strategy that can trick the immune system. Think of this strategy as having three phases, which each begin with the letter 'E' — elimination, equilibrium and escape.
In the elimination phase, your immune system sees the cancer and starts attacking it. This process depends enormously on various local and distant factors. These include what cells the cancer started in, in which part of the body it's located, what kind of cells and chemicals your immune system manufactures in response, and so on.
But the cancerous cells are continually mutating. From a genetic point of view, our cells are relatively stable. But cancer cells have several types of genetic instability seemingly built in - so their genome has enormous plasticity. This makes them effectively a moving target for your immune system. Your immune system can wipe out a percentage of the cancerous cells — but not all of them.
After the initial elimination phase, you reach the equilibrium phase. Here, there's a balance between the onslaught of the cancer, and the defence mounted by your immune system. If you're lucky, your immune system will be able to eventually eliminate all the cancer cells. If you're less lucky, you'll end up in a maintenance state, where the best you can do is keep the cancer the same size.
As an example, here's the strange story of a woman who had malignant melanoma, and who was 'successfully' treated for it. Sixteen years later she died — for reasons completely unrelated to the malignant melanoma. She was evaluated to be cancer-free at the time of her death. Therefore, each of her two healthy kidneys was transplanted into a willing recipient. However, everybody getting a kidney from a donor has to have their immune systems suppressed with drugs, so that their immune system won't reject the healthy kidneys. Within two years of the transplant, each recipient had come down with malignant melanoma.
It seems that the donor's healthy immune system had managed to control the malignant melanoma — and keep it in the equilibrium phase. But in the recipients, whose immune systems had been deliberately suppressed, the malignant melanoma cells ran amok.
Getting back to the three Es, if you're very unlucky, you'll enter the escape phase. (Now this is less exciting than it sounds, given that it's the cancer that escapes, not you!) Here, the immune system can no longer regulate the cancer cells, which escape from its control — and start spreading.
So what's happening on those incredibly rare occasions when the abscopal effect, kicks in? We still don't know the full picture.
But we are pretty sure that in the abscopal effect, somehow the immune system becomes more able to both recognise that a cancer is present, and also to attack that cancer.
For example, we know that radiation therapy increases the delivery of chemical markers of a cancer to the immune system. Then, via a long and complicated pathway, the immune system sends in the so-called 'killer T-cells' to knock off the cancer cells. But that's just one pathway, out of possibly hundreds or thousands
There is so much more to learn, and none of us should be immune to that ..