A recent study explores a vital yet often overlooked area in cancer research: Why does aging significantly increase the risk of cancer? The research uncovers how a declining immune system fuels tumor growth, providing new perspectives for preventing and treating cancer, particularly among older populations.
A groundbreaking study from the Icahn School of Medicine at Mount Sinai tackles an essential, yet inadequately studied, question in cancer research: Why is advancing age the primary risk factor for cancer? The findings show how an aging immune system contributes to tumor development, offering fresh insights for cancer prevention and treatment, especially pertinent to older adults.
Details of the research were published on September 5 in the Online First Release of Science. Using preclinical models, the team discovered that anakinra, a medication usually used to treat inflammatory conditions like rheumatoid arthritis, could be repurposed to interrupt harmful communication between early lung cancer lesions and the bone marrow. This interruption is crucial, the researchers assert, as an aging immune system tends to create harmful inflammation that may lead to cancer progression.
“The aging immune system incites damaging inflammation that fosters cancer growth by encouraging the buildup of pro-tumor macrophages, which are immune cells that inhibit the immune cells responsible for destroying tumor cells. This diminishes the body’s capacity to combat cancer,” explains Matthew D. Park, PhD, the study’s lead author and an MD/PhD student at Icahn Mount Sinai under the mentorship of senior corresponding author Miriam Merad, MD, PhD.
“By blocking specific inflammatory pathways, particularly those involving molecules known as interleukin-1⍺ (IL-1⍺) and IL-1β, we found that we could reverse this harmful cycle in mouse models, presenting a potential new strategy for preventing cancer in humans,” remarks Dr. Merad, who serves as Dean for Translational Research and Therapeutic Innovation, Director of the Marc and Jennifer Lipschultz Precision Immunology Institute, and Chair of Immunology and Immunotherapy at Icahn Mount Sinai.
The interaction between early lung cancer lesions and immune stem cells in the bone marrow via IL-1⍺/β significantly underscores the role of an aging immune system in promoting cancer growth.
Cancer increasingly affects individuals as they grow older, with the risk sharply escalating past the age of 60. While many hypotheses exist—ranging from accumulated environmental damage to genetic mutations—concrete evidence explaining the link between aging and cancer has been scarce, according to the researchers.
In their investigation, the researchers employed mouse models to examine the effect of aging on cancer progression. They injected tumor cells into mice and noted that lung, pancreatic, and colon cancers progressed more swiftly in the older mice than in their younger counterparts. By conducting bone marrow transplants from either young or elderly mice, the team simulated the impact of an aging immune system. They discovered that an older immune system hastens cancer growth, even in younger mice. Most notably, they found that rejuvenating the immune system led to a considerable decrease in cancer growth in older mice.
Through advanced analysis of cancer tissues from both mice and humans, the researchers pinpointed specific immune cells and factors that promote cancer growth in older adults. They successfully inhibited these elements, especially IL-1⍺/β, proving that targeting these molecules can diminish cancer advancement in older mice.
“Our research indicates that an aging immune system fosters cancer progress, independently of the cancer cells’ age or the surrounding tissues. We’ve long believed that inflammation could hinder anti-tumor immunity, especially in elderly patients with cancer. However, this is the first substantial evidence confirming that chronic inflammation resulting from an aging immune system can predispose individuals to cancer,” states Dr. Merad. “This study not only expands our lab’s focus to include immune aging but also sets the stage for future research on its connections to cancer and other age-related issues, including heart disease and infections.”
“Our findings suggest that targeting the aging immune system could significantly lower cancer risk among older individuals. It indicates that boosting the immune response via immunotherapy might be a more effective strategy than directly targeting tumors. The revelation that anakinra, which inhibits IL-1⍺/β and is already used to treat inflammatory conditions, can alleviate the detrimental impact of immune aging on cancer presents opportunities for repurposing existing drugs for cancer prevention,” comments co-senior author Thomas Marron, MD, PhD, Director of the Early Phase Trial Unit at Mount Sinai’s Tisch Cancer Institute. “We are now dedicated to translating these discoveries into clinical applications, having already designed early-phase clinical trials to test anakinra on high-risk patients.”
The ongoing clinical trials seek to determine whether focusing on the immune system can thwart cancer progression while the researchers continue to identify additional therapeutic targets. Their ultimate aim is to devise preventive strategies that minimize harmful inflammation in older adults, significantly lowering cancer rates.
