Melanoma progresses differently depending on age, according to research from Fox Chase Cancer Center presented at the American Association for Cancer Research annual meeting on Apr. 17. The study found that cancer spread was lowest in young mice, peaked in middle-aged mice, and declined again in very old mice.
This research highlights the importance of studying cancer across a broader range of ages. Most preclinical studies use young animals, even though cancer risk increases with age and tends to be more aggressive and harder to treat in older adults. This reliance on younger models may contribute to why many promising cancer drugs fail when tested in humans.
"The vast majority of studies are done in these very young mice that have a healthy and intact immune system," said Mitchell Fane, PhD, lead investigator of the study and a cancer biologist specializing in aging and cancer. "Right now, it's easy to personalize care for someone who's young and fit, who's potentially not going to experience as many toxicities; understanding how therapies affect older patients would give us more and better treatment options."
Fane's team identified gamma delta (γδ) T cells as an important factor influencing how melanoma spreads with age. Young and very old mice had higher levels of these immune cells, which appeared to keep the disease dormant or less likely to spread. Middle-aged mice had fewer γδ T cells; their cancers were more likely to metastasize aggressively. The researchers also found that melanoma can weaken the immune system by releasing molecules that exhaust γδ T cells—especially notable in middle-aged animals.
When γδ T cells were removed from young or very old mice, melanoma spread increased significantly. Blocking signals that suppress immunity restored protection against cancer but only worked for middle-aged animals.
One challenge facing aging research is cost: it takes up to two years for laboratory mice to reach an aged state suitable for experiments. To address this barrier, Fane and Yash Chabra, PhD—both Assistant Professors at Fox Chase—have set up an aged mouse facility providing researchers access to older animal models.
"Now we have a facility with established aged mouse colonies, which lowers the cost and time barriers to aging research," Fane said. "It allows us to tell colleagues, 'Your model is interesting, why not test it in aged mice?'"
The findings suggest further investigation into how aging impacts both tumor biology and patient outcomes could help develop better treatments tailored specifically for older individuals.
