London - When it comes to fighting cancer, do men have one hand tied behind their back? Women are far less likely to die from the deadly form of skin cancer melanoma, according to a report out last week. And experts suggest that part of the reason could be due to women’s more aggressive immune system.
“It’s generally accepted that women have a more responsive immune system,” says Professor Peter Johnson, chief clinician at Cancer Research UK. “They respond more reliably to vaccinations which work by activating the immune system. Fewer vaccinations ‘fail to take’ in women. Men’s immune systems, by contrast, are harder to stir up.”
What this means is that men’s immune systems are a bit less likely to clear away cells that are beginning to turn cancerous, or stop cells from a tumour spreading round the body. This is what could be happening with melanoma.
“This sort of cancer is particularly responsive to the state of the immune system,” explains Professor Johnson. “Men tend to have melanomas that have grown thicker by the time they are diagnosed, and they are more likely to come back.”
So why is a man’s internal defence system less alert?
One culprit is generally agreed to be testosterone which, besides being required for muscles, beards, square chins and a readiness to drive too fast and get into fights, also has the effect of damping down the immune system.
Several years ago, researchers at the famous Mayo Clinic in the US found that one way to boost the immune response in male mice was sharply to reduce their testosterone level. “It drives up the number of immune cells being produced,” commented the lead researcher.
“What’s more, the new immune cells in the testosterone-free mice are more aggressive and ready to attack than the ones the animals were producing earlier.”
Lowering testosterone also speeded up the time it took for their immune system to recover from chemotherapy.
So could men fighting cancer benefit from having their testosterone levels reduced, perhaps by a shot of oestrogen?
This certainly worked for mice in a study two years ago at the Massachusetts Institute of Technology in the US.
Men are more likely to develop stomach cancer than women and the study found that oestrogen had a protective effect. Female mice lose their protection when their ovaries are removed and the scientists found that male mice given oestrogen develop resistance to the disease.
However, the benefit of women’s hair-trigger immune defences has its downside - their immune system is so robust, it leads to a raised risk that their own organs will be damaged by friendly fire.
It’s long been known that auto-immune disorders (when the immune system starts attacking healthy cells), such as type 1 diabetes, multiple sclerosis and rheumatoid arthritis, are far more common in women.
All of these involve increased amounts of inflammation and now researchers at the University of Jena in Germany have found out how testosterone protects men from these diseases.
“Some immune cells in women produce twice as many inflammatory proteins as the same ones do in men,” says Dr Carlo Pergola, of the university’s Institute of Pharmacy. “Treating the enzyme producing these inflammatory proteins with testosterone brought production right down.” This could lead to new treatments for auto-immune disorders.
Another reason why women are more prone to auto-immune diseases could be down to the bacteria in their gut, according to a study published last week
“We’ve found a link between the different sex hormones and the colonies of bacteria that males and females have in their guts,” says Professor Alexander Chervonsky, of the Department of Pathology at the University of Chicago.
Professor Chervonsky’s laboratory has found that male and female mice have the same gut bacteria until they reach puberty and their hormones kick in. “This suggests that sex hormones contribute to gender-specific changes in microbial communities,” he says. In other words, the bacteria in men’s guts may damp down their immune systems so they don’t overreact, but the same is not happening for women.
Exactly why the main male sexual hormone should have a relaxing effect in the immune system is hotly debated.
But even though there are risks and benefits to having a less alert immune system, the female strategy seems to win in the end because women live longer.
And the latest research suggests that this isn’t just because of a more robust immune system thanks to more oestrogen and less testosterone.
Women seem to have two more things going for them. First, they keep their immune system troops on active duty for longer. A large study by Japanese researchers recently found that although we all produce fewer B-cells and T-cells - key players in the immune system - as we get older, the decline is more rapid in men than women.
Women also seem to be getting added protection from having two X chromosomes - which is what makes them women - while men have an X and a Y.
“Recently, we’ve found that the genes for making the T-cells that can target cancer cells are located on the X chromosome,” says Professor Johnson. “That gives women a better chance of having them available than men.”
So if men have a weaker immune system, does this mean man flu is real - ie, do men really suffer more from illness?
It’s a controversial area - recently the evidence seems to be swinging in favour of the existence of man flu, with two studies (one from the University of Queensland in Australia, the other from Queen Mary University of London) showing oestrogen protected women against viral infection, suggesting men might suffer more.
But just a few weeks ago, a report in the authoritative journal Nature suggested that the strength of their immune system means it is women who are worse off.
“Women are actually more likely to die as a result of infections,” said Professor Sabra Klein, an immunologist at Johns Hopkins Bloomberg School of Public Health and a leading expert on sex differences and infection.
“The very strength of their immune response means that their system gets flooded with all sorts of compounds that can cause trouble down the line.”
Klein’s research also suggests vaccination programmes should pay far more attention to the fact that the levels of sex hormones such as testosterone and oestrogen may alter how the immune system responds to threats. “Being on HRT or the contraceptive pill could make for a stronger immune response, for instance.”
At the moment, most experts believe it’s too early to change vaccination strategies - for men or women. So is there anything men can do to boost their immune system and put the fight on a more equal footing?
“The system is complicated and we are only just beginning to tease out all its twists and turns,” says Professor Johnson.
“Drugs that can stimulate the immune system, such as the new treatment for advanced melanoma - ipilimumab - have only recently been approved. It would be marvellous if you could get the same effect from taking a vitamin supplement, but you can’t.” - Daily Mail