Research suggests that mutations in ageing blood cells can influence how cancers grow, spread and respond to treatment.
Tumour cells (red) encircled by myeloid immune cells, including neutrophils (orange) and macrophages (yellow), which can promote inflammation and tumour progression.
Ageing leaves us with more than grey hairs and wrinkles, it’s etched into our DNA. The slow build‑up of genetic mutations in our cells and chronic inflammation is increasingly linked to a range of age‑related diseases, including cancer.
Charlie Swanton leads the Crick’s Cancer Evolution and Genome Instability Lab, where his team studies how cancer first develops and what drives it to spread to other parts of the body.
But why does cancer arise in the first place? And why does it become more common as we age?
To answer these questions, Charlie draws on his lessons from medical school and an old principle from turn-of-the-14th‑century monk William of Ockham, who said the simplest explanation is often the best.
“We’re used to thinking of age‑related conditions like neurodegeneration, cardiovascular disease and cancer as separate problems,” he says. “But maybe there’s a single upstream cause that links them all.”
Increasingly, labs like Charlie’s are studying a common process in which the immune system’s normal reactions continue to smoulder, at low levels, for much longer periods: chronic inflammation.
It’s an approach that guides his team’s work on environmental causes of cancer. They recently showed that air pollution can trigger lung cancer in people who have never smoked by sparking inflammation that awakens cells that already carry cancer‑causing mutations.
So, what happens as we age that increases our levels of chronic inflammation?
One phenomenon Crick researchers have been studying is the quiet accumulation of mutations in blood stem cells over time, known as clonal haematopoiesis of indeterminate potential (CHIP). It’s something that affects 10‑20% of us by the age of 70, and has already been linked to cardiovascular disease and other age‑related conditions.
However, other than linking it to leukaemia, researchers have only recently begun to study its role in cancer more broadly.
Equipped with data from more than 400 people with lung cancer, gathered as part of two long‑running Cancer Research UK‑funded studies, TRACERx and PEACE, they were able to show that lung cancer patients who carried CHIP mutations in their blood had significantly shorter survival times, regardless of their age or the stage at which their cancer was diagnosed.
Looking more deeply, they found that, in around half of the samples they studied, CHIP‑mutant blood cells had burrowed inside the tumour itself. This phenomenon, which they called tumour‑infiltrating clonal haematopoiesis (TI‑CH), was even more strongly linked to a patient’s chances of their cancer relapsing and dying from their cancer. And when they studied post-mortem samples from people whose tumours had spread, they found that these secondary tumours often contained TI‑CH cells too.
To confirm their findings, they teamed up researchers at Memorial Sloan Kettering Cancer Center in the US, who had access to a huge data set of over 22,000 patients with a range of cancer types. Once again, TI‑CH was linked to worse outcomes from cancer.
As Charlie says, “ageing blood may be a factor that’s actively shaping cancer evolution.”
At the heart of this process lies a biological fire known as ‘inflammaging’.
“Inflammaging is this persistent, low‑grade inflammation that comes with age,” Charlie explains. “We suspect that mutations in blood cells are combining with environmental exposures to release inflammatory molecules, quietly fuelling age‑related diseases.”
This is supported by another result from the CHIP study. The immune cells the team detected inside TI‑CH tumours were predominantly myeloid cells. Unlike some immune cells that are primed to recognise and fight cancer, myeloid cells have been shown to release molecules that regulate inflammation and can support tumours to grow and spread.
Further analysis of genes that were mutated in CHIP‑linked cancers highlighted TET2, which normally controls blood cell production. In lab‑grown tumours, TET2‑mutant myeloid cells accentuated the stem cell‑like qualities of cancer cells, which give them the ability to self‑renew and evolve. This helped explain how mutated immune cells might actively help tumours to grow.
There’s now growing realisation among scientists and doctors that ageing isn’t a passive backdrop to disease, but an active force that drives it.
“Studies that simply describe the complexity of cancer are one thing, but to really help patients we need to go further, and faster,” Charlie says.
For his team, the next steps are to study exactly how inflammatory pathways contribute to poor patient outcomes, particularly in the earliest stages of cancer development.
“What if our focus was not just on treating age‑related diseases but also cooling the chronic inflammation that might drive them?” Charlie adds.
“If we could target these processes, we might one day be able to slow inflammaging and, potentially, stall not only cancer, but a whole wave of age‑related conditions, allowing individuals to live longer healthier lives.”
