A new study from researchers at the Icahn School of Medicine at Mount Sinai has uncovered critical insights into why aging is the most significant risk factor for cancer. The research, published in Science, details how the aging immune system contributes to tumor growth and offers potential new avenues for cancer prevention, particularly for older adults.
Importantly, the team also identified an existing anti-inflammatory drug that could be used as a potential treatment. Working in pre-clinical models, the investigators found that the drug anakinra, which is typically used as a treatment for inflammatory conditions like rheumatoid arthritis, could be repurposed to block harmful signals between lung cancer lesions and the bone marrow.
“As the immune system ages, it triggers harmful inflammation that can drive cancer growth—by promoting the accumulation of pro-tumor macrophages, a type of immune cell that suppresses the immune effector cells that normally kill tumor cells. This weakens the body’s ability to fight cancer,” said Matthew D. Park, PhD, an MD/PhD student working in the Icahn School of Medicine lab of Miriam Merad, MD, PhD, chair of Immunology and Immunotherapy at Icahn Mount Sinai.
Added Merad, senior author of the study: “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.”
The study used mice to see the effects of aging on cancer progression. Tumor cells were injected into the mice, and the team noted that lung cancer, pancreatic cancer and colon cancer grew at a more rapid rate in older mice than it did in younger mice. To simulate the effects of an aging immune system, the researcher transplanted bone marrow from either old or young mice and discovered that the aged immune system accelerated cancer growth even in young mice. More importantly, however, the team also found that rejuvenating the immune system significantly slowed cancer growth rates in older mice.
“Our study shows that an aged immune system promotes cancer progression, independent of the age of the cancer cells or the surrounding tissue,” Merad said. “We’ve long suspected that inflammation can suppress anti-tumor immunity, particularly in older individuals and cancer patients. However, this is the first robust evidence proving that chronic inflammation from an aging immune system predisposes to cancer.”
Co-senior author Thomas Marron, MD, PhD, director of the Early Phase Trial Unit at Mount Sinai’s Tisch Cancer Institute, noted that these finding have broad clinical implications: “This study reveals that targeting the aging immune system could significantly reduce cancer risk in older adults. It suggests that enhancing the immune response through immunotherapy might be more effective than directly targeting tumors. The discovery that anakinra, which blocks the activity of IL-1⍺/β and is 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.”
The researchers are now focused on translating these findings into clinical practice and including the planned launch of an early-phase clinical trial for the use of anakinra in high-risk patients. In addition, they will explore additional therapeutic targets to reduce harmful inflammation for both cancer prevention and treatment strategies for aging populations.
