How ‘inflammaging’ could influence cancer treatment
Inflammation fuels the high rate of cancer in people over 50, researchers find, leading them to test anti-inflammatories such as allergy drugs to fight it.
People are more likely to get cancer as they age. Dr Miriam Merad has an unconventional idea of how that might be reversed: using allergy drugs and other seemingly unlikely medications to damp a condition known as “inflammaging”.
The immunologist and oncologist has spent years examining malignant tumours to learn why people over age 50 account for nine in 10 cancer diagnoses in the US.
She and her research team at the Icahn School of Medicine at Mount Sinai in New York City have homed in on an answer: the ageing immune system. Their studies of individual immune cells in human lung tumours, as well as in old mice, have revealed how chronic, or pathogenic, inflammation in older people – dubbed inflammaging – interferes with the immune system and fuels cancer growth.
Merad and other researchers are testing whether existing anti-inflammatory medications usually used to fight rheumatoid arthritis or allergy conditions like asthma or eczema can slow cancer in older patients. They are also searching for new drugs. “Ageing is something that we think we can transform,” says Dr Merad, director of the Marc and Jennifer Lipschultz Precision Immunology Institute at Mount Sinai.
Inflammation is the immune system’s reaction to a threat. Immune cells circulate in the body, attacking invaders such as viruses and cancer and calling for backup – more immune cells – when necessary. Working correctly, they can beat back Covid-19 or heal a cut on the finger. But the immune system can also overreact, fuelling inflammation that gets in the way of healing or leads to disease. It misfires like this more as people age.
“A big focus of the field right now is to separate beneficial inflammation, the one that protects us from microbes and from tumours, from the pathogenic inflammation that is enhancing cancer progression, promoting atherosclerosis, promoting damage in the older brain,” Dr Merad says.
The idea of using drugs on cancer patients that damp inflammation is counterintuitive, says Dr Andy Minn, who is scheduled to become chair of a new immuno-oncology program at Memorial Sloan Kettering Cancer Centre in August. Immunotherapies, which rev up the immune system to attack tumours, have transformed cancer care over the past several years. “The common wisdom is that we want to ramp up inflammation as much as possible so that inflammation can be harnessed by the immune system to kill the cancer,” Dr Minn says. “The blind spot has been that there are different types of inflammation.”
Often the assumption is that older people get sick more easily because their immune systems weaken, says Dr Thomas Marron, a thoracic medical oncologist who heads the early-phase trials unit at Mount Sinai’s Tisch Cancer Institute. That does happen, he says, but at the same time, “we really are seeing this sort of hyperactivation”.
“The body is just basically like a flower bed primed to grow cancer as you get older,” he says.
As a person ages, the immune system has to work harder to kill infections or mutations, like cancer. But the immune system itself is ageing and produces fewer of the type of immune cell that targets and kills cancer cells. At the same time, it makes more of a type of immune cell that responds initially to infections. Known as myeloid cells, with ageing they become more inclined to overreact and create inflammaging. These inflammatory cells may provide a “hit” necessary for older cells with mutations to turn cancerous, says Dr Merad of Mount Sinai.
A study of 72-week-old mice at Mount Sinai – correlating to about 65 years of age in humans – showed how an ageing immune system drives cancer. Matthew Park, a medical student who led the research in Dr Merad’s lab, discovered that myeloid cells in lung tumours of the older mice churned out interleukin-1, or IL-1, a protein long linked to inflammaging. The IL-1 summoned more myeloid cells to the lungs, leading to more inflammation and tumour growth.
When Mr Park put young immune systems in the mice, their lung cancer came under control.
He also gave the mice a rheumatoid-arthritis drug called anakinra that blocks IL-1. It slowed tumour growth when given early. That suggests that anti-inflammatory treatment would work best for older people at high risk of cancer, or with early-stage disease, according to the study, although research findings on mice can’t always be generalised to humans. “We can potentially prevent lung cancer,” Mr Park says.
Drugs known as JAK inhibitors – used to treat inflammatory diseases like eczema or ulcerative colitis – have similar potential for treating cancer in older patients, two studies published in June 2024 suggest. One study examined patients with lung cancer. The other showed that a drug called ruxolitinib stopped Hodgkin lymphoma from progressing in 46 per cent of patients who were also on immunotherapy.
Treatment in the future will involve using technology to figure out when to fire up the immune system or quiet it, says John Teijaro, professor of immunology and microbiology at the Scripps Research Institute in La Jolla, California.
“It’s not as simple as you either turn on the gas or hit the brake,” says Professor Teijaro, co-senior author of the ruxolitinib study.
Marron at Mount Sinai is testing another type of medication in older cancer patients – an antiviral – to combat inflammaging. The hope is to calm inflammation that flares up when ancient viruses that are integrated into the human genome reactivate, which can happen during ageing.
Anne Martz, a 90-year-old with metastatic lung cancer, participated in a trial last fall of lamivudine, an antiviral for HIV and hepatitis B. It had shown a benefit in the 72-week-old mice in Dr Merad’s lab.
Ms Martz, who was born in Denmark and lives in New York City, had a recurrence of lung cancer three years ago and has been receiving immunotherapy. It beat back much of the cancer, she said, but a tumour grew on her adrenal gland and the immunotherapy wasn’t working against it.
After she took the lamivudine pills twice a day for six weeks, along with her immunotherapy, a scan showed the tumour stopped growing. She is back on the lamivudine pills now after a more recent scan showed growth again.
She likes that the drug was tested in older mice. ”I thought if it had been in elderly mice, I’m an elderly person, it might work with me, too,” she said.
The Wall Street Journal
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