How the aging immune system fuels cancer growth

A new study by researchers at the Icahn School of Medicine at Mount Sinai addresses a critical yet under-explored question in cancer research: why is aging the biggest risk factor for cancer? The team’s findings, published in the journal Science, reveal how an aging immune system spurs tumour growth, offering new insights into cancer prevention and treatment — especially for older adults.

Cancer is a disease that becomes increasingly common as we age, with the risk rising sharply after the age of 60. Many theories have been proposed, including the cumulative effects of environmentally induced damage and genetic mutations, but there has been little concrete data explaining why aging drives cancer.

In order to investigate how aging affects cancer progression, the research team injected tumour cells into mice and observed that lung, pancreatic and colonic cancer grew more rapidly in older mice compared to younger ones. Using bone marrow transplants from either young or old mice, the investigators simulated the effects of the immune system’s aging. The team found that an aged immune system accelerates cancer growth, even in young mice. More strikingly, they found that rejuvenating the immune system significantly reduced cancer growth in older mice.

“As the immune system ages, it triggers harmful inflammation that can drive cancer growth by promoting the accumulation of pro-tumour macrophages — a type of immune cell that suppresses the immune effector cells that normally kill tumour cells,” said lead author Matthew D Park, PhD, a sixth-year Icahn Mount Sinai MD/PhD student. “This weakens the body’s ability to fight cancer.”

Using high-dimensional analysis of murine and human cancer tissues, the team identified specific cells and immune-related factors that accelerate cancer growth in the elderly. They then successfully blocked these factors in preclinical models by repurposing the drug anakinra — which reduced cancer growth in the aged mice.

“We found that by blocking specific inflammatory pathways, especially those involving molecules called interleukin-1⍺ (IL-1⍺) and IL-1β, this damaging process could be reversed in mouse models, offering a potential new approach to preventing cancer development in humans,” said Dr Miriam Merad, senior corresponding author on the study.

Merad said scientists have long suspected that inflammation can suppress anti-tumour immunity, particularly in older individuals and cancer patients, but this is the first robust evidence proving that chronic inflammation from an aging immune system promotes cancer progression — independent of the age of the cancer cells or the surrounding tissue.

“This research not only brings our lab into the field of immune aging but also lays the groundwork for future studies, exploring its links to cancer and other aging-related conditions like cardiovascular disease and infections.”

“This study reveals that targeting the aging immune system could significantly reduce cancer risk in older adults,” added co-senior author Dr Thomas Marron, who suggested that enhancing the immune response through immunotherapy might be more effective than directly targeting tumours.

“The discovery that anakinra, which blocks the activity of IL-1⍺/β and is a drug already used for inflammatory conditions, can mitigate the harmful effects of immune aging on cancer opens the door to repurposing existing medications for cancer prevention,” he said. “We’re now focused on translating these findings into clinical practice … [and] have now designed early-phase clinical trials to use anakinra in high-risk patients.”

Image credit: iStock.com/FatCamera