New study reveals how aging immune system promotes cancer growth, potentially opening new avenues for prevention

A new study by researchers at the Icahn School of Medicine at Mount Sinai addresses a critical but underexplored question in cancer research: Why is aging the greatest risk factor for cancer? The study reveals how an aging immune system drives tumor growth, offering new insights into cancer prevention and treatment, particularly in older adults.

Details of the results are reported in the first online version of September 5 Science. In preclinical models, the research team found that anakinra, a drug typically used to treat inflammatory diseases such as rheumatoid arthritis, can be repurposed to block harmful signals between early lung cancer lesions and the bone marrow. This is critical, the researchers say, because as the immune system ages, it creates harmful inflammation that can promote cancer growth.

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

“We discovered that by blocking specific inflammatory pathways, particularly 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. Merad, dean of translational research and therapeutic innovation, director of the Marc and Jennifer Lipschultz Precision Immunology Institute, and chair of the department of immunology and immunotherapy at Icahn Mount Sinai.

Cancer is a disease that becomes more common with age, with the risk increasing sharply after age 60. Many theories have been proposed, including the cumulative effects of environmental damage and genetic mutations, but there is little hard data explaining why aging promotes cancer, researchers say.

In this study, the research team used mouse models to study the effect of aging on cancer progression. They injected tumor cells into mice and observed that lung, pancreatic, and colon cancers grew faster in older mice than in younger ones. Using bone marrow transplants from both young and old mice, the researchers simulated the effects of aging on the immune system. The team found that an aging immune system accelerates cancer growth, even in young mice. Even more striking, they found that rejuvenating the immune system significantly reduced cancer growth in older mice.

Using high-dimensional analysis of mouse and human cancer tissues, the team identified specific cells and immune factors that accelerate cancer growth in older adults. They then successfully blocked these factors, particularly IL-1⍺/β, demonstrating that inhibiting these molecules can reduce cancer growth in older mice.

“Our study shows that an aging immune system promotes cancer progression, regardless of the age of the cancer cells or surrounding tissues. We have long suspected that inflammation can suppress antitumor immunity, particularly in older adults and cancer patients. However, this is the first strong evidence that chronic inflammation due to aging of the immune system predisposes to cancer,” says Dr. Merad. “This research not only allows our laboratory to focus on immune aging, but also lays the foundation for future studies exploring its links to cancer and other age-related diseases such as cardiovascular disease and infections.”

“This study shows that targeting the aging immune system could significantly reduce cancer risk in older adults. It suggests that enhancing the immune response through immunotherapy may be more effective than targeting tumors directly. The discovery that anakinra, which blocks IL-1⍺/β activity and is a drug already used for inflammatory diseases, can mitigate the harmful effects of immune aging on cancer opens the door to repurposing existing drugs for cancer prevention,” said co-senior author Thomas Marron, MD, PhD, director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai. “We are now focused on translating these findings into clinical practice. Based on these results, we have now designed early-phase clinical trials to use anakinra in high-risk patients.”

Ongoing trials are aimed at determining whether targeting the immune system can prevent cancer progression, while researchers continue to explore other therapeutic targets. Their ultimate goal is to develop preventative measures that reduce harmful inflammation in older adults, thereby significantly reducing the incidence of cancer.