Cancer risk increases with age and is often more aggressive and difficult to treat in older people. However, less than 10% of mouse studies use older animals, and most rely on mice roughly equivalent to humans in their early 20s. This discrepancy is one potential reason why many anticancer drugs that have shown promise in preclinical models continue to fail in human trials.
New research from Fox Chase Cancer Center presented at the American Association for Cancer Research annual meeting suggests that melanoma behaves differently with age. The data showed that cancer spread was lowest in young mice, peaked in middle-aged mice, and decreased in very old mice.
“The majority of the research has been done in very young mice with healthy, intact immune systems,” said Dr. Mitchell Fehn, a cancer biologist who specializes in aging and cancer and the study’s principal investigator. “Right now, it’s easy to customize care for patients who are young, healthy, and may not experience many toxicities. If we can understand how treatments affect older patients, we’ll have more and better treatment options.”
Fehn and colleagues suggest that a key factor behind their discovery involves a specific group of immune cells called gamma delta (γδ) T cells. This group acts like an early warning guard to prevent the spread of cancer. Young and very old mice had more of these protective immune cells, and their cancers were more likely to remain dormant or less likely to spread. Middle-aged mice had fewer γδ T cells and their melanomas were much more likely to spread to organs such as the lungs and liver.
The study also showed that melanoma cells themselves can actively weaken the immune system as the animals age. In middle-aged mice, melanomas released specific molecules that shut down or depleted γδ T cells, allowing previously silent cancer cells to “wake up” and actively spread.
Remarkably, when the researchers removed γδ T cells from young and very old mice, the spread of melanoma increased, suggesting that these immune cells normally help suppress cancer. In contrast, blocking immunosuppressive signals restored immune defenses and reduced cancer spread, but only in middle-aged mice.
More comprehensive mouse model
One reason why so few studies use older mice is that younger mice are cheaper and more readily available. Mice must be housed and cared for approximately 18 to 24 months until they are old enough for geriatric mouse models.
Fehn and colleague Dr. Yash Chhabra, both assistant professors in the Cancer Signaling and Microenvironment Research Program, helped establish the Aged Mouse Facility at Fox Chase. Together, they are giving researchers access to better models of how cancer behaves in older patients.
“We now have facilities with established colonies of aging mice, which lowers the cost and time barriers for aging research,” he said. “This allows me to say to my colleagues, ‘Your model is interesting, why don’t you test it on aging mice?'”
Individualized care for elderly patients
A better understanding of the role of aging in cancer is an important step toward developing better treatments for older patients. Fehn’s lab is also interested in how the relationship between cancer risk and age is not linear.
The risk increases steadily with age but decreases sharply after age 80 to 85. We would like to explain the mechanism behind why cancer incidence among middle-aged patients is increasing while cancer incidence among very elderly patients is decreasing. ”
Dr. Mitchell Fehn, Cancer Biologist
sauce:
Temple University Health System
Reference magazines:
Coutant, K. others. (2026). Summary 2072: The role of aging in gamma radiation d ;T cells in the progression of metastatic cutaneous melanoma Cancer research. DOI: 10.1158/1538-7445.AM2026-2072. https://aacrjournals.org/cancerres/article/86/7_Supplement/2072/777378/Abstract-2072-Role-of-the-aging-on-the-T-cells-in
